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William H. Griffith - One of the best experts on this subject based on the ideXlab platform.
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Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment
Journal of Neurophysiology, 2009Co-Authors: David Murchison, Angelika N. Mcdermott, Candi L. Lasarge, Kathryn A. Peebles, Jennifer L. Bizon, William H. GriffithAbstract:Alterations in neuronal Ca2+ homeostasis are important determinants of age-related cognitive impairment. We examined the Ca2+ influx, Buffering, and electrophysiology of basal forebrain neurons in adult, middle-aged, and aged male F344 behaviorally assessed rats. Middle-aged and aged rats were characterized as cognitively impaired or unimpaired by water maze performance relative to young cohorts. Patch-clamp experiments were conducted on neurons acutely dissociated from medial septum/nucleus of the diagonal band with post hoc identification of phenotypic marker mRNA using single-cell RT-PCR. We measured whole cell Calcium and barium currents and dissected these currents using pharmacological agents. We combined Ca2+ current recording with Ca2+-sensitive ratiometric microfluorimetry to measure Ca2+ Buffering. Additionally, we sought changes in neuronal firing properties using current-clamp recording. There were no age- or cognition-related changes in the amplitudes or fractional compositions of the whole cell Ca2+ channel currents. However, Ca2+ Buffering was significantly enhanced in cholinergic neurons from aged cognitively impaired rats. Moreover, increased Ca2+ Buffering was present in middle-aged rats that were not cognitively impaired. Firing properties were largely unchanged with age or cognitive status, except for an increase in the slow afterhyperpolarization in aged cholinergic neurons, independent of cognitive status. Furthermore, acutely dissociated basal forebrain neurons in which choline acetyltransferase mRNA was detected had the electrophysiological profiles of identified cholinergic neurons. We conclude that enhanced Ca2+ Buffering by cholinergic basal forebrain neurons may be important during aging.
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Calcium Buffering systems and Calcium signaling in aged rat basal forebrain neurons
Aging Cell, 2007Co-Authors: David Murchison, William H. GriffithAbstract:Disturbances of neuronal Ca2+ homeostasis are considered to be important determinants of age-related cognitive impairment. Cholinergic neurons of the basal forebrain (BF) are principal targets of decline associated with aging and dementia. During the last several years, we have attempted to link these concepts in a rat model of 'normal' aging. In this review, we will describe some changes that we have observed in Ca2+ signaling of aged BF neurons and the reversal of one of these changes by dietary caloric restriction. Our evidence supports a scenario in which subtle changes in the properties of voltage-gated Ca2+ channels result in increased Ca2+ influx during aging. This increased Ca2+, in turn, triggers an increase in rapid Ca2+ Buffering in the somatic compartment of aged BF neurons. However, this nominal 'compensation', along with other changes in Ca2+ handling machinery (notably mitochondria) alters the Ca2+ signal with age in a way that is dependent on the magnitude of the Ca2+ load. By combining whole-cell patch clamp electrophysiology, ratiometric Ca2+-sensitive microfluorimetry and single-cell reverse transcription-polymerase chain reaction, we have determined that age-related rapid Buffering changes are present in identified cholinergic BF neurons and that these changes can be prevented by a caloric restriction dietary regimen. Because caloric restriction extends lifespan and retards the progression of age-related dysfunction, these findings suggest that increased Ca2+ Buffering in cholinergic neurons may be relevant to cognitive decline during normal aging. Importantly, Calcium homeostatic mechanisms of BF cholinergic neurons are amenable to dietary interventions that could promote cognitive health during aging.
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age related alterations in caffeine sensitive Calcium stores and mitochondrial Buffering in rat basal forebrain
Cell Calcium, 1999Co-Authors: David Murchison, William H. GriffithAbstract:The properties of caffeine- and thapsigargin-sensitive endoplasmic reticulum Calcium stores were compared in acutely dissociated basal forebrain neurons from young and aged F344 rats by ratiometric microfluorimetry. The ability of these stores to sequester and release Calcium resembles that observed in other central neurons, with an important role of mitochondrial Calcium Buffering in regulating the response to caffeine. An age-related reduction in the filling state of the stores in resting cells appears to be mediated by increased rapid Calcium Buffering, which reduces the availability of Calcium for uptake into the stores. An age-related decrease in the amplitude of maximal caffeine-induced Calcium release was attributed to increased mitochondrial Buffering. There were no age-related differences in the sensitivity to caffeine or in the Calcium sequestration/release process at the level of the endoplasmic reticulum per se. These findings demonstrate the importance of interactions between cellular Calcium Buffering mechanisms and provide details regarding age-related changes in Calcium homeostasis which have been thought to occur in these and other neurons associated with age-related neuronal dysfunctions.
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increased Calcium Buffering in basal forebrain neurons during aging
Journal of Neurophysiology, 1998Co-Authors: David Murchison, William H. GriffithAbstract:Increased Calcium Buffering in basal forebrain neurons during aging. J. Neurophysiol. 80: 350-364, 1998. Alterations of neuronal Calcium (Ca2+) homeostasis are thought to underlie many age-related changes in the nervous system. Basal forebrain neurons are susceptible to changes associated with aging and to related dysfunctions such as Alzheimer's disease. It recently was shown that neurons from the medial septum and nucleus of the diagonal band (MS/nDB) of aged (24-27 mo) F344 rats have an increased current influx through voltage-gated Ca2+ channels (VGCCs) relative to those of young (1-4. 5 mo) rats. Possible age-related changes in Ca2+ Buffering in these neurons have been investigated using conventional whole cell and perforated-patch voltage clamp combined with fura-2 microfluorimetric techniques. Basal intracellular Ca2+ concentrations ([Ca2+]i), Ca2+ influx, Ca2+ transients (Delta[Ca2+]i), and time course of Delta[Ca2+]i were quantitated, and rapid Ca2+ Buffering values were calculated in MS/nDB neurons from young and aged rats. The involvement of the smooth endoplasmic reticulum (SER) was examined with the SER Ca2+ uptake blocker, thapsigargin. An age-related increase in rapid Ca2+ Buffering and Delta[Ca2+]i time course was observed, although basal [Ca2+]i was unchanged with age. The SER and endogenous diffusible Buffering mechanisms were found to have roles in Ca2+ Buffering, but they did not mediate the age-related changes. These findings suggest a model in which some aging central neurons could compensate for increased Ca2+ influx with greater Ca2+ Buffering.
David Murchison - One of the best experts on this subject based on the ideXlab platform.
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Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment
Journal of Neurophysiology, 2009Co-Authors: David Murchison, Angelika N. Mcdermott, Candi L. Lasarge, Kathryn A. Peebles, Jennifer L. Bizon, William H. GriffithAbstract:Alterations in neuronal Ca2+ homeostasis are important determinants of age-related cognitive impairment. We examined the Ca2+ influx, Buffering, and electrophysiology of basal forebrain neurons in adult, middle-aged, and aged male F344 behaviorally assessed rats. Middle-aged and aged rats were characterized as cognitively impaired or unimpaired by water maze performance relative to young cohorts. Patch-clamp experiments were conducted on neurons acutely dissociated from medial septum/nucleus of the diagonal band with post hoc identification of phenotypic marker mRNA using single-cell RT-PCR. We measured whole cell Calcium and barium currents and dissected these currents using pharmacological agents. We combined Ca2+ current recording with Ca2+-sensitive ratiometric microfluorimetry to measure Ca2+ Buffering. Additionally, we sought changes in neuronal firing properties using current-clamp recording. There were no age- or cognition-related changes in the amplitudes or fractional compositions of the whole cell Ca2+ channel currents. However, Ca2+ Buffering was significantly enhanced in cholinergic neurons from aged cognitively impaired rats. Moreover, increased Ca2+ Buffering was present in middle-aged rats that were not cognitively impaired. Firing properties were largely unchanged with age or cognitive status, except for an increase in the slow afterhyperpolarization in aged cholinergic neurons, independent of cognitive status. Furthermore, acutely dissociated basal forebrain neurons in which choline acetyltransferase mRNA was detected had the electrophysiological profiles of identified cholinergic neurons. We conclude that enhanced Ca2+ Buffering by cholinergic basal forebrain neurons may be important during aging.
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Calcium Buffering systems and Calcium signaling in aged rat basal forebrain neurons
Aging Cell, 2007Co-Authors: David Murchison, William H. GriffithAbstract:Disturbances of neuronal Ca2+ homeostasis are considered to be important determinants of age-related cognitive impairment. Cholinergic neurons of the basal forebrain (BF) are principal targets of decline associated with aging and dementia. During the last several years, we have attempted to link these concepts in a rat model of 'normal' aging. In this review, we will describe some changes that we have observed in Ca2+ signaling of aged BF neurons and the reversal of one of these changes by dietary caloric restriction. Our evidence supports a scenario in which subtle changes in the properties of voltage-gated Ca2+ channels result in increased Ca2+ influx during aging. This increased Ca2+, in turn, triggers an increase in rapid Ca2+ Buffering in the somatic compartment of aged BF neurons. However, this nominal 'compensation', along with other changes in Ca2+ handling machinery (notably mitochondria) alters the Ca2+ signal with age in a way that is dependent on the magnitude of the Ca2+ load. By combining whole-cell patch clamp electrophysiology, ratiometric Ca2+-sensitive microfluorimetry and single-cell reverse transcription-polymerase chain reaction, we have determined that age-related rapid Buffering changes are present in identified cholinergic BF neurons and that these changes can be prevented by a caloric restriction dietary regimen. Because caloric restriction extends lifespan and retards the progression of age-related dysfunction, these findings suggest that increased Ca2+ Buffering in cholinergic neurons may be relevant to cognitive decline during normal aging. Importantly, Calcium homeostatic mechanisms of BF cholinergic neurons are amenable to dietary interventions that could promote cognitive health during aging.
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age related alterations in caffeine sensitive Calcium stores and mitochondrial Buffering in rat basal forebrain
Cell Calcium, 1999Co-Authors: David Murchison, William H. GriffithAbstract:The properties of caffeine- and thapsigargin-sensitive endoplasmic reticulum Calcium stores were compared in acutely dissociated basal forebrain neurons from young and aged F344 rats by ratiometric microfluorimetry. The ability of these stores to sequester and release Calcium resembles that observed in other central neurons, with an important role of mitochondrial Calcium Buffering in regulating the response to caffeine. An age-related reduction in the filling state of the stores in resting cells appears to be mediated by increased rapid Calcium Buffering, which reduces the availability of Calcium for uptake into the stores. An age-related decrease in the amplitude of maximal caffeine-induced Calcium release was attributed to increased mitochondrial Buffering. There were no age-related differences in the sensitivity to caffeine or in the Calcium sequestration/release process at the level of the endoplasmic reticulum per se. These findings demonstrate the importance of interactions between cellular Calcium Buffering mechanisms and provide details regarding age-related changes in Calcium homeostasis which have been thought to occur in these and other neurons associated with age-related neuronal dysfunctions.
-
increased Calcium Buffering in basal forebrain neurons during aging
Journal of Neurophysiology, 1998Co-Authors: David Murchison, William H. GriffithAbstract:Increased Calcium Buffering in basal forebrain neurons during aging. J. Neurophysiol. 80: 350-364, 1998. Alterations of neuronal Calcium (Ca2+) homeostasis are thought to underlie many age-related changes in the nervous system. Basal forebrain neurons are susceptible to changes associated with aging and to related dysfunctions such as Alzheimer's disease. It recently was shown that neurons from the medial septum and nucleus of the diagonal band (MS/nDB) of aged (24-27 mo) F344 rats have an increased current influx through voltage-gated Ca2+ channels (VGCCs) relative to those of young (1-4. 5 mo) rats. Possible age-related changes in Ca2+ Buffering in these neurons have been investigated using conventional whole cell and perforated-patch voltage clamp combined with fura-2 microfluorimetric techniques. Basal intracellular Ca2+ concentrations ([Ca2+]i), Ca2+ influx, Ca2+ transients (Delta[Ca2+]i), and time course of Delta[Ca2+]i were quantitated, and rapid Ca2+ Buffering values were calculated in MS/nDB neurons from young and aged rats. The involvement of the smooth endoplasmic reticulum (SER) was examined with the SER Ca2+ uptake blocker, thapsigargin. An age-related increase in rapid Ca2+ Buffering and Delta[Ca2+]i time course was observed, although basal [Ca2+]i was unchanged with age. The SER and endogenous diffusible Buffering mechanisms were found to have roles in Ca2+ Buffering, but they did not mediate the age-related changes. These findings suggest a model in which some aging central neurons could compensate for increased Ca2+ influx with greater Ca2+ Buffering.
Sue P. Duckles - One of the best experts on this subject based on the ideXlab platform.
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serca function declines with age in adrenergic nerves from the superior cervical ganglion
Journal of Autonomic Pharmacology, 2000Co-Authors: W. J. Pottorf, Sue P. Duckles, John N. BuchholzAbstract:1 Intracellular Calcium is a universal second messenger integrating numerous cellular pathways. An age-related breakdown in the mechanisms controlling [Ca2+]i homeostasis could contribute to neuronal degeneration. One component of neuronal Calcium regulation believed to decline with age is the function of sarco/endoplasmic reticulum Calcium ATPase (SERCA) pumps. 2 Therefore we investigated the impact of age on the capacity of SERCA pumps to control high (68 m M) [K+]-evoked [Ca2+]i-transients in acutely dissociated superior cervical ganglion (SCG) cells from 6- and 20-month-old Fisher-344 rats. Calcium transients were measured by fura-2 microfluorometry in the presence of vanadate (0.1 μM) to selectively block plasma membrane Calcium ATPase (PMCA) pumps, dinitrophenol (100 μM) to block mitochondrial Calcium uptake and extracellular sodium replaced with tetraethylammonium to block Na+/Ca2+-exchanger, thus forcing the neuronal cells to rely on SERCA uptake to control [Ca2+]i homeostasis. 3 In the presence of these Calcium Buffering blockers, the rate of recovery of [Ca2+]i was significantly slower and time to recover to approximately 90% of resting [Ca2+]i was significantly greater in SCG cells from old (20 months) compared with young (6 months) animals. 4 This age-related change in the recovery phase of [K+]-evoked [Ca2+]i-transients could not be explained by differences in the sensitivity of SCG cells to the Calcium Buffering blockers, as no age-related difference in basal [Ca2+]i was observed. 5 These studies illustrate that when rat SCG cells are forced to rely on SERCAs to buffer [K+]-evoked [Ca2+]i-transients, an age-related decline in SERCA function is revealed. Such age-related declines in Calcium regulation coupled with neuronal sensitivity to Calcium overload underscore the importance of understanding the components of [Ca2+]i homeostasis and the functional compensation that may occur with advancing age.
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adrenergic nerves compensate for a decline in Calcium Buffering during ageing
Journal of Autonomic Pharmacology, 2000Co-Authors: W. J. Pottorf, Sue P. Duckles, John N. BuchholzAbstract:1. The ubiquitous involvement of intracellular Calcium ([Ca2+]i) in multiple neuronal pathways has led investigators to suggest that dysfunction of Calcium homeostasis may be the primary mediator of age-related neuronal degeneration. Recently, it was shown that sympathetic neurones from superior cervical ganglion (SCG) of aged rats demonstrate decreased sarco-/endoplasmic reticulum Ca2+-ATPase (SERCA) function and that aged neurones are more dependent upon mitochondria to control K+-evoked [Ca2+]i transients. 2. Therefore, in the present study we investigated age-related changes in ATP-dependent Calcium pumps of plasma membrane Ca2+-ATPase (PMCA) and SERCA in acutely dissociated SCG cells from Fischer-344 rats aged 6 and 20 months. To distinguish between PMCA and SERCA pump activity, we applied the Ca2+-ATPase blocker vanadate and measured rates of recovery of K+-evoked [Ca2+]i transients by fura-2 microfluorometry. 3. Young SCG cells showed a biphasic response to vanadate over the vanadate concentration range (0.01-100 microM); however, old SCG cells showed only a single response over the same concentration range. Additionally, old SCG cells showed a greater sensitivity to Ca2+-ATPase blockade by vanadate. 4. The contribution of mitochondrial Calcium uptake to regulate [Ca2+]i was also investigated. To measure the impact of mitochondrial Calcium uptake, PMCAs and SERCAs were blocked with vanadate (100 microM) and extracellular sodium was replaced with tetraethylammonium (TEA) to block Na+/Ca2+-exchange. Treated SCG cells showed a decline of 50% in rate of recovery of [Ca2+]i in both 6- and 20-month-old cells; however, this effect did not vary with age. 5. These data suggest that there is an age-related decline in function of SERCAs, with an increased reliance on PMCAs to control high K+-evoked [Ca2+]i transients. In addition, there appears to be no age-related change in the capacity of the mitochondria to restore [Ca2+]i transients to basal levels.
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Adrenergic Nerve Smooth Endoplasmic Reticulum Calcium Buffering Declines with Age
Neurobiology of Aging, 1998Co-Authors: Henry Tsai, W. J. Pottorf, John N. Buchholz, Sue P. DucklesAbstract:Calcium Buffering capacity declines with age in sympathetic nerves of rat tail artery. To test whether smooth endoplasmic reticulum (SER) Calcium Buffering declines with age, effects of two SER Calcium-ATPase inhibitors on norepinephrine release and intracellular Calcium were determined. Thapsigargin or cyclopiazonic acid caused a significant increase in stimulation-evoked norepinephrine release from 6 month tail arteries with much less effect in 20 months. In isolated superior cervical ganglion cells, the rate of rise of Calcium with K+-depolarization increased only in young cells with either cyclopiazonic acid or thapsigargin, with no effect in the old. In young cells, cyclopiazonic acid significantly influenced time to peak, rate of decline, and time to basal of K+-evoked Calcium transients, but had no effect in old cells. Thapsigargin caused a significant increase in rate of decline in young, but not old, cells. These differential effects suggest an age-related decline in function of SER Calcium Buffering mechanisms in the sympathetic nervous system causing older nerves to become more reliant on mitochondria to buffer Calcium.
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intracellular Calcium Buffering declines in aging adrenergic nerves
Neurobiology of Aging, 1997Co-Authors: Henry Tsai, John N. Buchholz, C W Hewitt, Sue P. DucklesAbstract:Stimulation-evoked norepinephrine release from rat tail artery adrenergic nerves increased with advancing age in the Fischer-344 rat when function of norepinephrine uptake mechanisms and prejunctional alpha-2 adrenoceptors were blocked. When Calcium channels were bypassed with the ionophore, ionomycin (4 microM), norepinephrine release from aged nerves (20 months) was still elevated as compared to 6-month-old nerves. Norepinephrine release stimulated by high K+ was also higher in 20-month nerves. The intracellular Calcium chelator, 1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetomethylester (BAPTA/AM), was used to determine whether age-related increases in norepinephrine release could be reversed with the addition of an artificial intracellular Calcium buffer. Exposure to BAPTA/AM decreased stimulation-evoked norepinephrine release in both old and young tail arteries; however, the effect was significantly greater in older arteries. When mitochondrial Calcium uptake was compromised using the uncoupler of mitochondrial oxidative phosphorylation, dinitrophenol, BAPTA caused a further decrease in stimulation-evoked norepinephrine release in 20-month tail arteries with much less effect in 6-month-old nerves. These results suggest that intracellular Calcium Buffering is less efficient in older nerves.
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advancing age alters intracellular Calcium Buffering in rat adrenergic nerves
Neurobiology of Aging, 1996Co-Authors: John N. Buchholz, Henry Tsai, Sylvain Foucart, Sue P. DucklesAbstract:There is a marked increase with advancing age of stimulation-evoked neurotransmitter release from vascular adrenergic nerves in the rat, an effect correlated with increased levels of plasma norepinephrine. This increase in norepinephrine release could not be accounted for by an alteration in neuronal and extraneuronal uptake of norepinephrine or a decline in feedback inhibition of release by prejunctional alpha2-adrenergic receptors. Measurement of intracellular Calcium in fura-2-labeled superior cervical ganglion cells revealed elevated K+-evoked Calcium transients in old compared to young neurons. Blockade of mitochondrial Calcium uptake with dinitrophenol resulted in increased Calcium transients in old neurons only. Furthermore, following blockade of mitochondrial Calcium uptake the rate of return of Calcium to resting levels was reduced to a greater degree in old cells as compared to young cells. The effects of dinitrophenol in old cells were attenuated when extracellular Calcium was reduced. These findings suggest that older cells are more dependent on mitochondrial Calcium Buffering, perhaps due to changes in ATP dependent Calcium uptake. Increased Calcium transients as a result of altered intracellular Calcium Buffering offer a reasonable explanation for our previous observation of increased stimulation evoked norepinephrine release.
John N. Buchholz - One of the best experts on this subject based on the ideXlab platform.
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serca function declines with age in adrenergic nerves from the superior cervical ganglion
Journal of Autonomic Pharmacology, 2000Co-Authors: W. J. Pottorf, Sue P. Duckles, John N. BuchholzAbstract:1 Intracellular Calcium is a universal second messenger integrating numerous cellular pathways. An age-related breakdown in the mechanisms controlling [Ca2+]i homeostasis could contribute to neuronal degeneration. One component of neuronal Calcium regulation believed to decline with age is the function of sarco/endoplasmic reticulum Calcium ATPase (SERCA) pumps. 2 Therefore we investigated the impact of age on the capacity of SERCA pumps to control high (68 m M) [K+]-evoked [Ca2+]i-transients in acutely dissociated superior cervical ganglion (SCG) cells from 6- and 20-month-old Fisher-344 rats. Calcium transients were measured by fura-2 microfluorometry in the presence of vanadate (0.1 μM) to selectively block plasma membrane Calcium ATPase (PMCA) pumps, dinitrophenol (100 μM) to block mitochondrial Calcium uptake and extracellular sodium replaced with tetraethylammonium to block Na+/Ca2+-exchanger, thus forcing the neuronal cells to rely on SERCA uptake to control [Ca2+]i homeostasis. 3 In the presence of these Calcium Buffering blockers, the rate of recovery of [Ca2+]i was significantly slower and time to recover to approximately 90% of resting [Ca2+]i was significantly greater in SCG cells from old (20 months) compared with young (6 months) animals. 4 This age-related change in the recovery phase of [K+]-evoked [Ca2+]i-transients could not be explained by differences in the sensitivity of SCG cells to the Calcium Buffering blockers, as no age-related difference in basal [Ca2+]i was observed. 5 These studies illustrate that when rat SCG cells are forced to rely on SERCAs to buffer [K+]-evoked [Ca2+]i-transients, an age-related decline in SERCA function is revealed. Such age-related declines in Calcium regulation coupled with neuronal sensitivity to Calcium overload underscore the importance of understanding the components of [Ca2+]i homeostasis and the functional compensation that may occur with advancing age.
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adrenergic nerves compensate for a decline in Calcium Buffering during ageing
Journal of Autonomic Pharmacology, 2000Co-Authors: W. J. Pottorf, Sue P. Duckles, John N. BuchholzAbstract:1. The ubiquitous involvement of intracellular Calcium ([Ca2+]i) in multiple neuronal pathways has led investigators to suggest that dysfunction of Calcium homeostasis may be the primary mediator of age-related neuronal degeneration. Recently, it was shown that sympathetic neurones from superior cervical ganglion (SCG) of aged rats demonstrate decreased sarco-/endoplasmic reticulum Ca2+-ATPase (SERCA) function and that aged neurones are more dependent upon mitochondria to control K+-evoked [Ca2+]i transients. 2. Therefore, in the present study we investigated age-related changes in ATP-dependent Calcium pumps of plasma membrane Ca2+-ATPase (PMCA) and SERCA in acutely dissociated SCG cells from Fischer-344 rats aged 6 and 20 months. To distinguish between PMCA and SERCA pump activity, we applied the Ca2+-ATPase blocker vanadate and measured rates of recovery of K+-evoked [Ca2+]i transients by fura-2 microfluorometry. 3. Young SCG cells showed a biphasic response to vanadate over the vanadate concentration range (0.01-100 microM); however, old SCG cells showed only a single response over the same concentration range. Additionally, old SCG cells showed a greater sensitivity to Ca2+-ATPase blockade by vanadate. 4. The contribution of mitochondrial Calcium uptake to regulate [Ca2+]i was also investigated. To measure the impact of mitochondrial Calcium uptake, PMCAs and SERCAs were blocked with vanadate (100 microM) and extracellular sodium was replaced with tetraethylammonium (TEA) to block Na+/Ca2+-exchange. Treated SCG cells showed a decline of 50% in rate of recovery of [Ca2+]i in both 6- and 20-month-old cells; however, this effect did not vary with age. 5. These data suggest that there is an age-related decline in function of SERCAs, with an increased reliance on PMCAs to control high K+-evoked [Ca2+]i transients. In addition, there appears to be no age-related change in the capacity of the mitochondria to restore [Ca2+]i transients to basal levels.
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Adrenergic Nerve Smooth Endoplasmic Reticulum Calcium Buffering Declines with Age
Neurobiology of Aging, 1998Co-Authors: Henry Tsai, W. J. Pottorf, John N. Buchholz, Sue P. DucklesAbstract:Calcium Buffering capacity declines with age in sympathetic nerves of rat tail artery. To test whether smooth endoplasmic reticulum (SER) Calcium Buffering declines with age, effects of two SER Calcium-ATPase inhibitors on norepinephrine release and intracellular Calcium were determined. Thapsigargin or cyclopiazonic acid caused a significant increase in stimulation-evoked norepinephrine release from 6 month tail arteries with much less effect in 20 months. In isolated superior cervical ganglion cells, the rate of rise of Calcium with K+-depolarization increased only in young cells with either cyclopiazonic acid or thapsigargin, with no effect in the old. In young cells, cyclopiazonic acid significantly influenced time to peak, rate of decline, and time to basal of K+-evoked Calcium transients, but had no effect in old cells. Thapsigargin caused a significant increase in rate of decline in young, but not old, cells. These differential effects suggest an age-related decline in function of SER Calcium Buffering mechanisms in the sympathetic nervous system causing older nerves to become more reliant on mitochondria to buffer Calcium.
-
intracellular Calcium Buffering declines in aging adrenergic nerves
Neurobiology of Aging, 1997Co-Authors: Henry Tsai, John N. Buchholz, C W Hewitt, Sue P. DucklesAbstract:Stimulation-evoked norepinephrine release from rat tail artery adrenergic nerves increased with advancing age in the Fischer-344 rat when function of norepinephrine uptake mechanisms and prejunctional alpha-2 adrenoceptors were blocked. When Calcium channels were bypassed with the ionophore, ionomycin (4 microM), norepinephrine release from aged nerves (20 months) was still elevated as compared to 6-month-old nerves. Norepinephrine release stimulated by high K+ was also higher in 20-month nerves. The intracellular Calcium chelator, 1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetomethylester (BAPTA/AM), was used to determine whether age-related increases in norepinephrine release could be reversed with the addition of an artificial intracellular Calcium buffer. Exposure to BAPTA/AM decreased stimulation-evoked norepinephrine release in both old and young tail arteries; however, the effect was significantly greater in older arteries. When mitochondrial Calcium uptake was compromised using the uncoupler of mitochondrial oxidative phosphorylation, dinitrophenol, BAPTA caused a further decrease in stimulation-evoked norepinephrine release in 20-month tail arteries with much less effect in 6-month-old nerves. These results suggest that intracellular Calcium Buffering is less efficient in older nerves.
-
advancing age alters intracellular Calcium Buffering in rat adrenergic nerves
Neurobiology of Aging, 1996Co-Authors: John N. Buchholz, Henry Tsai, Sylvain Foucart, Sue P. DucklesAbstract:There is a marked increase with advancing age of stimulation-evoked neurotransmitter release from vascular adrenergic nerves in the rat, an effect correlated with increased levels of plasma norepinephrine. This increase in norepinephrine release could not be accounted for by an alteration in neuronal and extraneuronal uptake of norepinephrine or a decline in feedback inhibition of release by prejunctional alpha2-adrenergic receptors. Measurement of intracellular Calcium in fura-2-labeled superior cervical ganglion cells revealed elevated K+-evoked Calcium transients in old compared to young neurons. Blockade of mitochondrial Calcium uptake with dinitrophenol resulted in increased Calcium transients in old neurons only. Furthermore, following blockade of mitochondrial Calcium uptake the rate of return of Calcium to resting levels was reduced to a greater degree in old cells as compared to young cells. The effects of dinitrophenol in old cells were attenuated when extracellular Calcium was reduced. These findings suggest that older cells are more dependent on mitochondrial Calcium Buffering, perhaps due to changes in ATP dependent Calcium uptake. Increased Calcium transients as a result of altered intracellular Calcium Buffering offer a reasonable explanation for our previous observation of increased stimulation evoked norepinephrine release.
Henry Tsai - One of the best experts on this subject based on the ideXlab platform.
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Adrenergic Nerve Smooth Endoplasmic Reticulum Calcium Buffering Declines with Age
Neurobiology of Aging, 1998Co-Authors: Henry Tsai, W. J. Pottorf, John N. Buchholz, Sue P. DucklesAbstract:Calcium Buffering capacity declines with age in sympathetic nerves of rat tail artery. To test whether smooth endoplasmic reticulum (SER) Calcium Buffering declines with age, effects of two SER Calcium-ATPase inhibitors on norepinephrine release and intracellular Calcium were determined. Thapsigargin or cyclopiazonic acid caused a significant increase in stimulation-evoked norepinephrine release from 6 month tail arteries with much less effect in 20 months. In isolated superior cervical ganglion cells, the rate of rise of Calcium with K+-depolarization increased only in young cells with either cyclopiazonic acid or thapsigargin, with no effect in the old. In young cells, cyclopiazonic acid significantly influenced time to peak, rate of decline, and time to basal of K+-evoked Calcium transients, but had no effect in old cells. Thapsigargin caused a significant increase in rate of decline in young, but not old, cells. These differential effects suggest an age-related decline in function of SER Calcium Buffering mechanisms in the sympathetic nervous system causing older nerves to become more reliant on mitochondria to buffer Calcium.
-
intracellular Calcium Buffering declines in aging adrenergic nerves
Neurobiology of Aging, 1997Co-Authors: Henry Tsai, John N. Buchholz, C W Hewitt, Sue P. DucklesAbstract:Stimulation-evoked norepinephrine release from rat tail artery adrenergic nerves increased with advancing age in the Fischer-344 rat when function of norepinephrine uptake mechanisms and prejunctional alpha-2 adrenoceptors were blocked. When Calcium channels were bypassed with the ionophore, ionomycin (4 microM), norepinephrine release from aged nerves (20 months) was still elevated as compared to 6-month-old nerves. Norepinephrine release stimulated by high K+ was also higher in 20-month nerves. The intracellular Calcium chelator, 1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetomethylester (BAPTA/AM), was used to determine whether age-related increases in norepinephrine release could be reversed with the addition of an artificial intracellular Calcium buffer. Exposure to BAPTA/AM decreased stimulation-evoked norepinephrine release in both old and young tail arteries; however, the effect was significantly greater in older arteries. When mitochondrial Calcium uptake was compromised using the uncoupler of mitochondrial oxidative phosphorylation, dinitrophenol, BAPTA caused a further decrease in stimulation-evoked norepinephrine release in 20-month tail arteries with much less effect in 6-month-old nerves. These results suggest that intracellular Calcium Buffering is less efficient in older nerves.
-
advancing age alters intracellular Calcium Buffering in rat adrenergic nerves
Neurobiology of Aging, 1996Co-Authors: John N. Buchholz, Henry Tsai, Sylvain Foucart, Sue P. DucklesAbstract:There is a marked increase with advancing age of stimulation-evoked neurotransmitter release from vascular adrenergic nerves in the rat, an effect correlated with increased levels of plasma norepinephrine. This increase in norepinephrine release could not be accounted for by an alteration in neuronal and extraneuronal uptake of norepinephrine or a decline in feedback inhibition of release by prejunctional alpha2-adrenergic receptors. Measurement of intracellular Calcium in fura-2-labeled superior cervical ganglion cells revealed elevated K+-evoked Calcium transients in old compared to young neurons. Blockade of mitochondrial Calcium uptake with dinitrophenol resulted in increased Calcium transients in old neurons only. Furthermore, following blockade of mitochondrial Calcium uptake the rate of return of Calcium to resting levels was reduced to a greater degree in old cells as compared to young cells. The effects of dinitrophenol in old cells were attenuated when extracellular Calcium was reduced. These findings suggest that older cells are more dependent on mitochondrial Calcium Buffering, perhaps due to changes in ATP dependent Calcium uptake. Increased Calcium transients as a result of altered intracellular Calcium Buffering offer a reasonable explanation for our previous observation of increased stimulation evoked norepinephrine release.