The Experts below are selected from a list of 1068 Experts worldwide ranked by ideXlab platform
Christopher L-h. Huang - One of the best experts on this subject based on the ideXlab platform.
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Detubulation abolishes membrane potential stabilization in amphibian skeletal muscle.
Journal of muscle research and cell motility, 2020Co-Authors: Diana X-l Chin, James A Fraser, Juliet A Usher-smith, Jeremy N Skepper, Christopher L-h. HuangAbstract:A recently reported stabilization ('splinting') of the resting membrane potential ( Em) observed in amphibian skeletal muscle fibres despite Extracellular hyperosmotic challenge has been attributed to high resting ratios of membrane Cl- to K+ permeability ( P Cl/ P K) combined with elevations of their intracellular Cl- concentrations, [Cl-]i, above electrochemical equilibrium by diuretic-sensitive cation-Cl-, Na-Cl (NCC) and/or Na-K-2Cl (NKCC), co-transporter activity. The present experiments localized this co-transporter activity by investigating the effects of established detubulation procedures on Em splinting. They exposed fibres to introduction and subsequent withdrawal of 400 mM Extracellular glycerol, high divalent cation concentrations, and cooling. An abolition of tubular access of Extracellularly added lissamine rhodamine fluorescence, visualized by confocal microscopy, and of the action potential afterdepolarization together confirmed successful transverse (T-) tubular detachment. Fibre volumes, V , of such detubulated fibres, determined using recently introduced confocal microscope-scanning methods, retained the simple dependence upon 1/[Extracellular Osmolarity], without significant evidence of the regulatory volume increases described in other cell types, previously established in intact fibres. However detubulation abolished the Em splinting shown by intact fibres. Em thus varied with Extracellular Osmolarity in detubulated fibres studied in standard, Cl(-)-containing, Ringer solutions and conformed to simple predictions from such changes in assuming that intracellular ion content was conserved and membrane potential change DeltaEm was principally determined by the K+ Nernst potential. Furthermore, cation--Cl- co-transport block brought about by [Cl-]o or [Na+]o deprivation, or inclusion of bumetanide (10 microM) and chlorothiazide (10 microM) in the Extracellular fluid gave similar results. When taken together with previous reports of significant Cl- conductances in the surface membrane, these findings suggest a model that contrastingly suggests a T-tubular location for cation--Cl- co-transporter activity or its regulation.
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Detubulation abolishes membrane potential stabilization in amphibian skeletal muscle
Journal of Muscle Research and Cell Motility, 2020Co-Authors: Diana X-l Chin, James A Fraser, Juliet A Usher-smith, Jeremy N Skepper, Christopher L-h. HuangAbstract:A recently reported stabilization (`splinting') of the resting membrane potential (Em) observed in amphibian skeletal muscle fibres despite Extracellular hyperosmotic challenge has been attributed to high resting ratios of membrane Cl− to K+ permeability (PCl/PK) combined with elevations of their intracellular Cl− concentrations, [Cl−]i, above electrochemical equilibrium by diuretic-sensitive cation--Cl−, Na--Cl (NCC) and/or Na--K--2Cl (NKCC), co-transporter activity. The present experiments localized this co-transporter activity by investigating the effects of established detubulation procedures on Em splinting. They exposed fibres to introduction and subsequent withdrawal of 400 mM Extracellular glycerol, high divalent cation concentrations, and cooling. An abolition of tubular access of Extracellularly added lissamine rhodamine fluorescence, visualized by confocal microscopy, and of the action potential afterdepolarization together confirmed successful transverse (T-) tubular detachment. Fibre volumes, V, of such detubulated fibres, determined using recently introduced confocal microscope-scanning methods, retained the simple dependence upon 1/[Extracellular Osmolarity], without significant evidence of the regulatory volume increases described in other cell types, previously established in intact fibres. However detubulation abolished the Em splinting shown by intact fibres. m thus varied with Extracellular Osmolarity in detubulated fibres studied in standard, Cl−-containing, Ringer solutions and conformed to simple predictions from such changes in assuming that intracellular ion content was conserved and membrane potential change ΔEm was principally determined by the K+ Nernst potential. Furthermore, cation--Cl− co-transport block brought about by [Cl−]o or [Na+]o deprivation, or inclusion of bumetanide (10 μM) and chlorothiazide (10 μM) in the Extracellular fluid gave similar results. When taken together with previous reports of significant Cl− conductances in the surface membrane, these findings suggest a model that contrastingly suggests a T-tubular location for cation--Cl− co-transporter activity or its regulation.
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Conduction velocities in amphibian skeletal muscle fibres exposed to hyperosmotic Extracellular solutions.
Journal of Muscle Research and Cell Motility, 2007Co-Authors: Zhongbo Chen, Sandeep S. Hothi, Wei Xu, Christopher L-h. HuangAbstract:Early quantitative analyses of conduction velocities in unmyelinated nerve studied in a constantly iso-osmotic volume conductor were extended to an analysis of the effects of varying Extracellular osmolarities on conduction velocities of surface membrane action potentials in Rana esculenta skeletal muscle fibres. Previous papers had reported that skeletal muscle fibres exposed to a wide range of Extracellular sucrose concentrations resemble perfect osmometers with increased Extracellular Osmolarity proportionally decreasing fibre volume and therefore diminishing fibre radius, a. However, classical electrolyte theory (Robinson and Stokes 1959, Electrolyte solutions 2nd edn. Butterworth & Co. pp 41–42) would then predict that the consequent increases in intracellular ionic strength would correspondingly decrease sarcoplasmic resistivity, Ri. An extension of the original cable analysis then demonstrated that the latter would precisely offset its expected effect of alterations in a on the fibre axial resistance, ri, and leave action potential conduction velocity constant. In contrast, other reports (Hodgkin and Nakajima J Physiol 221:105–120, 1972) had suggested that Riincreased with Extracellular Osmolarity, owing to alterations in cytosolic viscosity. This led to a prediction of a decreased conduction velocity. These opposing hypotheses were then tested in muscle fibres subject to just-suprathreshold stimulation at a Vaseline seal at one end and measuring action potentials and their first order derivatives, dV/dt, using 5–20 MΩ, 3 M KCl glass microelectrodes at defined distances away from the stimulus sites. Exposures to hyperosmotic, sucrose-containing, Ringer solutions then reversibly reduced both conduction velocity and maximum values of dV/dt. This was compatible with an increase in Ri in the event that conduction depended upon a discharge of membrane capacitance by propagating local circuit currents through initially passive electrical elements. Conduction velocity then showed graded decreases with increasing Extracellular Osmolarity from 250–750 mOsm. Action potential waveforms through these Osmolarity changes remained similar, including both early surface and the late after-depolarisation events reflecting transverse tubular activation. Quantitative comparisons of reduced-χ 2 values derived from a comparison of these results and the differing predictions from the two hypotheses strongly favoured the hypothesis in which Riincreased rather than decreased with hyperOsmolarity. Electronic supplementary material The online version of this article (doi:10.1007/s10974-007-9115-8) contains supplementary material, which is available to authorized users.
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Conduction velocities in amphibian skeletal muscle fibres exposed to hyperosmotic Extracellular solutions.
Journal of muscle research and cell motility, 2007Co-Authors: Zhongbo Chen, Sandeep S. Hothi, Wei Xu, Christopher L-h. HuangAbstract:Early quantitative analyses of conduction velocities in unmyelinated nerve studied in a constantly iso-osmotic volume conductor were extended to an analysis of the effects of varying Extracellular osmolarities on conduction velocities of surface membrane action potentials in Rana esculenta skeletal muscle fibres. Previous papers had reported that skeletal muscle fibres exposed to a wide range of Extracellular sucrose concentrations resemble perfect osmometers with increased Extracellular Osmolarity proportionally decreasing fibre volume and therefore diminishing fibre radius, a. However, classical electrolyte theory (Robinson and Stokes 1959, Electrolyte solutions 2nd edn. Butterworth & Co. pp 41-42) would then predict that the consequent increases in intracellular ionic strength would correspondingly decrease sarcoplasmic resistivity, R(i). An extension of the original cable analysis then demonstrated that the latter would precisely offset its expected effect of alterations in a on the fibre axial resistance, r(i), and leave action potential conduction velocity constant. In contrast, other reports (Hodgkin and Nakajima J Physiol 221:105-120, 1972) had suggested that R(i) increased with Extracellular Osmolarity, owing to alterations in cytosolic viscosity. This led to a prediction of a decreased conduction velocity. These opposing hypotheses were then tested in muscle fibres subject to just-suprathreshold stimulation at a Vaseline seal at one end and measuring action potentials and their first order derivatives, dV/dt, using 5-20 MOmega, 3 M KCl glass microelectrodes at defined distances away from the stimulus sites. Exposures to hyperosmotic, sucrose-containing, Ringer solutions then reversibly reduced both conduction velocity and maximum values of dV/dt. This was compatible with an increase in R(i) in the event that conduction depended upon a discharge of membrane capacitance by propagating local circuit currents through initially passive electrical elements. Conduction velocity then showed graded decreases with increasing Extracellular Osmolarity from 250-750 mOsm. Action potential waveforms through these Osmolarity changes remained similar, including both early surface and the late after-depolarisation events reflecting transverse tubular activation. Quantitative comparisons of reduced-chi(2) values derived from a comparison of these results and the differing predictions from the two hypotheses strongly favoured the hypothesis in which R(i) increased rather than decreased with hyperOsmolarity.
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Conduction velocities in amphibian skeletal muscle fibres exposed to hyperosmotic Extracellular solutions
Journal of Muscle Research and Cell Motility, 2007Co-Authors: Zhongbo Chen, Sandeep S. Hothi, Wei Xu, Christopher L-h. HuangAbstract:Early quantitative analyses of conduction velocities in unmyelinated nerve studied in a constantly iso-osmotic volume conductor were extended to an analysis of the effects of varying Extracellular osmolarities on conduction velocities of surface membrane action potentials in Rana esculenta skeletal muscle fibres. Previous papers had reported that skeletal muscle fibres exposed to a wide range of Extracellular sucrose concentrations resemble perfect osmometers with increased Extracellular Osmolarity proportionally decreasing fibre volume and therefore diminishing fibre radius, a . However, classical electrolyte theory (Robinson and Stokes 1959, Electrolyte solutions 2nd edn. Butterworth & Co. pp 41–42) would then predict that the consequent increases in intracellular ionic strength would correspondingly decrease sarcoplasmic resistivity, R _ i . An extension of the original cable analysis then demonstrated that the latter would precisely offset its expected effect of alterations in a on the fibre axial resistance, r _ i , and leave action potential conduction velocity constant . In contrast, other reports (Hodgkin and Nakajima J Physiol 221:105–120, 1972) had suggested that R _ i increased with Extracellular Osmolarity, owing to alterations in cytosolic viscosity. This led to a prediction of a decreased conduction velocity. These opposing hypotheses were then tested in muscle fibres subject to just-suprathreshold stimulation at a Vaseline seal at one end and measuring action potentials and their first order derivatives, d V /d t , using 5–20 MΩ, 3 M KCl glass microelectrodes at defined distances away from the stimulus sites. Exposures to hyperosmotic, sucrose-containing, Ringer solutions then reversibly reduced both conduction velocity and maximum values of d V /d t . This was compatible with an increase in R _ i in the event that conduction depended upon a discharge of membrane capacitance by propagating local circuit currents through initially passive electrical elements. Conduction velocity then showed graded decreases with increasing Extracellular Osmolarity from 250–750 mOsm. Action potential waveforms through these Osmolarity changes remained similar, including both early surface and the late after-depolarisation events reflecting transverse tubular activation. Quantitative comparisons of reduced-χ ^2 values derived from a comparison of these results and the differing predictions from the two hypotheses strongly favoured the hypothesis in which R _ i increased rather than decreased with hyperOsmolarity.
Michael C. Gustin - One of the best experts on this subject based on the ideXlab platform.
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a second osmosensing signal transduction pathway in yeast hypotonic shock activates the pkc1 protein kinase regulated cell integrity pathway
Journal of Biological Chemistry, 1995Co-Authors: Kenneth R Davenport, David E. Levin, Michael Sohaskey, Yoshiaki Kamada, Michael C. GustinAbstract:Abstract Yeast cells respond to hypertonic shock by activation of a (MAP) mitogen-activated protein kinase cascade called the (HOG) high Osmolarity glycerol response pathway. How yeast respond to hypotonic shock is unknown. Results of this investigation show that a second MAP kinase cascade in yeast called the protein kinase C1 (PKC1) pathway is activated by hypotonic shock. Tyrosine phosphorylation of the PKC1 pathway MAP kinase increased rapidly in cells following a shift of the external medium to lower Osmolarity. The intensity of the response was proportional to the magnitude of the decrease in Extracellular Osmolarity. This response to hypotonic shock required upstream protein kinases of the PKC1 pathway. Increasing external Osmolarity inhibited tyrosine phosphorylation of the PKC1 pathway MAP kinase, a response that was blocked by BCK1-20, a constitutively active mutant in an upstream protein kinase. These results indicate that yeast contain two osmosensing signal transduction pathways, the HOG pathway and the PKC1 pathway, that respond to hypertonic and hypotonic shock, respectively.
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An osmosensing signal transduction pathway in yeast.
Science, 1993Co-Authors: Jay L. Brewster, T De Valoir, Noelle D. Dwyer, Edward Winter, Michael C. GustinAbstract:Yeast genes were isolated that are required for restoring the osmotic gradient across the cell membrane in response to increased external Osmolarity. Two of these genes, HOG1 and PBS2, encode members of the mitogen-activated protein kinase (MAP kinase) and MAP kinase kinase gene families, respectively. MAP kinases are activated by Extracellular ligands such as growth factors and function as intermediate kinases in protein phosphorylation cascades. A rapid, PBS2-dependent tyrosine phosphorylation of HOG1 protein occurred in response to increases in Extracellular Osmolarity. These data define a signal transduction pathway that is activated by changes in the Osmolarity of the Extracellular environment.
Makarand V Risbud - One of the best experts on this subject based on the ideXlab platform.
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nucleus pulposus primary cilia alter their length in response to changes in Extracellular Osmolarity but do not control tonebp mediated osmoregulation
Scientific Reports, 2019Co-Authors: Hyowon Choi, Irving M Shapiro, Vedavathi Madhu, Makarand V RisbudAbstract:The nucleus pulposus (NP) cells adapt to their physiologically hyperosmotic microenvironment through Tonicity-responsive enhancer binding protein (TonEBP/nuclear factor of activated T-cell5 [NFAT5])-mediated osmoregulation. Primary cilia in different organs serve diverse roles including osmosensing, but its contribution to NP cell osmoadaptive response is unknown. A high percentage of cultured primary NP cells possessed primary cilia that changed length in response to osmotic stimuli. Stable silencing of Intraflagellar Transport 88 (Ift88) or Kinesin Family Member 3 A (Kif3a) to inhibit the formation of primary cilia did not affect hyperosmotic upregulation of TonEBP. While ShKif3a blocked hyperosmotic increase of TonEBP-Transactivation Domain (TAD) activity, overall the knockdown of either gene did not alter the hyperosmotic status of proximal promoter activities and transcription of key TonEBP targets. On the other hand, a small decrease in TonEBP level under hypoosmotic condition was attenuated by Ift88 or Kif3a knockdown. Noteworthy, none of the TonEBP target genes were responsive to hypoosmotic stimulus in control and Ift88 or Kif3a knockdown cells, suggesting the primary role of TonEBP in the hyperosmotic adaptation of NP cells. Similarly, in Kif3a null mouse embryonic fibroblasts (MEFs), the overall TonEBP-dependent hyperosmotic responses were preserved. Unlike NP cells, TonEBP targets were responsive to hypoOsmolarity in wild-type MEFs, and these responses remained intact in Kif3a null MEFs. Together, these results suggest that primary cilia are dispensable for TonEBP-dependent osmoadaptive response.
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Extracellular Osmolarity regulates matrix homeostasis in the intervertebral disc and articular cartilage evolving role of tonebp
Matrix Biology, 2014Co-Authors: Zariel I Johnson, Irving M Shapiro, Makarand V RisbudAbstract:Degeneration of the intervertebral disc is characterized by changes in proteoglycan status, loss of bound water molecules, decreased tissue osmotic pressure and a resulting mechanical failure of the disc. A similar spectrum of changes is evident in osteoarthritic articular cartilage. When healthy, resident cells in these skeletal tissues respond to applied mechanical loads by regulating their own osmotic state and the hydration of the Extracellular matrix. The transcription factor Tonicity-Responsive Enhancer Binding Protein (TonEBP or NFAT5) is known to mediate the osmoadaptive response in these and other tissues. While the molecular basis of how osmotic loading controls matrix homeostasis is not completely understood, TonEBP regulates the expression of aggrecan and β1,3-glucoronosyltransferase in nucleus pulposus cells, in addition to targets that allow for survival under hypertonic stress. Moreover, in chondrocytes, TonEBP controls expression of several collagen subtypes and Sox9, a master regulator of aggrecan and collagen II expression. Thus, TonEBP-mediated regulation of the matrix composition allows disc cells and chondrocytes to modify the Extracellular osmotic state itself. On the other hand, TonEBP in immune cells induces expression of TNF-α, IL-6 and MCP-1, pro-inflammatory molecules closely linked to matrix catabolism and pathogenesis of both disc degeneration and osteoarthritis, warranting investigations of this aspect of TonEBP function in skeletal cells. In summary, the TonEBP system, through its effects on Extracellular matrix and osmoregulatory genes can be viewed primarily as a protective or homeostatic response to physiological loading.
Massimiliano G Bianchi - One of the best experts on this subject based on the ideXlab platform.
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protein kinase r mediates the inflammatory response induced by hyperosmotic stress
Molecular and Cellular Biology, 2017Co-Authors: Kenneth T Farabaugh, Dawid Krokowski, Bo Jhih Guan, Mithu Majumder, Andrew Schuster, Edward D. Chan, Raul Jobava, Jing Wu, Michelle S Longworth, Massimiliano G BianchiAbstract:Abstract High Extracellular Osmolarity results in a switch from an adaptive to an inflammatory gene expression program. We show that hyperosmotic stress activates the protein kinase R (PKR) independently of its RNA-binding domain. In turn, PKR stimulates nuclear accumulation of nuclear factor κB (NF-κB) p65 species phosphorylated at serine-536, which is paralleled by the induction of a subset of inflammatory NF-κB p65-responsive genes, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and IL-1β. The PKR-mediated hyperinduction of iNOS decreases cell survival in mouse embryonic fibroblasts via mechanisms involving nitric oxide (NO) synthesis and posttranslational modification of proteins. Moreover, we demonstrate that the PKR inhibitor C16 ameliorates both iNOS amplification and disease-induced phenotypic breakdown of the intestinal epithelial barrier caused by an increase in Extracellular Osmolarity induced by dextran sodium sulfate (DSS) in vivo Collectively, these findings indicate that PKR activation is an essential part of the molecular switch from adaptation to inflammation in response to hyperosmotic stress.
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coordinated regulation of the neutral amino acid transporter snat2 and the protein phosphatase subunit gadd34 promotes adaptation to increased Extracellular Osmolarity
Journal of Biological Chemistry, 2015Co-Authors: Dawid Krokowski, Bo Jhih Guan, Martin D. Snider, Kenneth T Farabaugh, Mithu Majumder, Raul Jobava, Massimiliano G Bianchi, Jing Wu, Ovidio Bussolati, Maria HatzoglouAbstract:Abstract Cells respond to shrinkage induced by increased Extracellular Osmolarity via programmed changes in gene transcription and mRNA translation. The immediate response to this stress includes the induction of expression of the neutral amino acid transporter SNAT2. Increased SNAT2-mediated uptake of neutral amino acids is an essential adaptive mechanism for restoring cell volume. In contrast, stress-induced phosphorylation of the α subunit of the translation initiation factor eIF2 (eIF2α) can promote apoptosis. Here we show that the response to mild hyperosmotic stress involves regulation of the phosphorylation of eIF2α by increased levels of GADD34, a regulatory subunit of protein phosphatase 1 (PP1). The induction of GADD34 was dependent on transcriptional control by the c-Jun-binding cAMP response element in the GADD34 gene promoter and posttranscriptional stabilization of its mRNA. This mechanism differs from the regulation of GADD34 expression by other stresses that involve activating transcription factor 4 (ATF4). ATF4 was not translated during hyperosmotic stress despite an increase in eIF2α phosphorylation. The SNAT2-mediated increase in amino acid uptake was enhanced by increased GADD34 levels in a manner involving decreased eIF2α phosphorylation. It is proposed that the induction of the SNAT2/GADD34 axis enhances cell survival by promoting the immediate adaptive response to stress.
Zhongbo Chen - One of the best experts on this subject based on the ideXlab platform.
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Conduction velocities in amphibian skeletal muscle fibres exposed to hyperosmotic Extracellular solutions.
Journal of muscle research and cell motility, 2007Co-Authors: Zhongbo Chen, Sandeep S. Hothi, Wei Xu, Christopher L-h. HuangAbstract:Early quantitative analyses of conduction velocities in unmyelinated nerve studied in a constantly iso-osmotic volume conductor were extended to an analysis of the effects of varying Extracellular osmolarities on conduction velocities of surface membrane action potentials in Rana esculenta skeletal muscle fibres. Previous papers had reported that skeletal muscle fibres exposed to a wide range of Extracellular sucrose concentrations resemble perfect osmometers with increased Extracellular Osmolarity proportionally decreasing fibre volume and therefore diminishing fibre radius, a. However, classical electrolyte theory (Robinson and Stokes 1959, Electrolyte solutions 2nd edn. Butterworth & Co. pp 41-42) would then predict that the consequent increases in intracellular ionic strength would correspondingly decrease sarcoplasmic resistivity, R(i). An extension of the original cable analysis then demonstrated that the latter would precisely offset its expected effect of alterations in a on the fibre axial resistance, r(i), and leave action potential conduction velocity constant. In contrast, other reports (Hodgkin and Nakajima J Physiol 221:105-120, 1972) had suggested that R(i) increased with Extracellular Osmolarity, owing to alterations in cytosolic viscosity. This led to a prediction of a decreased conduction velocity. These opposing hypotheses were then tested in muscle fibres subject to just-suprathreshold stimulation at a Vaseline seal at one end and measuring action potentials and their first order derivatives, dV/dt, using 5-20 MOmega, 3 M KCl glass microelectrodes at defined distances away from the stimulus sites. Exposures to hyperosmotic, sucrose-containing, Ringer solutions then reversibly reduced both conduction velocity and maximum values of dV/dt. This was compatible with an increase in R(i) in the event that conduction depended upon a discharge of membrane capacitance by propagating local circuit currents through initially passive electrical elements. Conduction velocity then showed graded decreases with increasing Extracellular Osmolarity from 250-750 mOsm. Action potential waveforms through these Osmolarity changes remained similar, including both early surface and the late after-depolarisation events reflecting transverse tubular activation. Quantitative comparisons of reduced-chi(2) values derived from a comparison of these results and the differing predictions from the two hypotheses strongly favoured the hypothesis in which R(i) increased rather than decreased with hyperOsmolarity.
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Conduction velocities in amphibian skeletal muscle fibres exposed to hyperosmotic Extracellular solutions.
Journal of Muscle Research and Cell Motility, 2007Co-Authors: Zhongbo Chen, Sandeep S. Hothi, Wei Xu, Christopher L-h. HuangAbstract:Early quantitative analyses of conduction velocities in unmyelinated nerve studied in a constantly iso-osmotic volume conductor were extended to an analysis of the effects of varying Extracellular osmolarities on conduction velocities of surface membrane action potentials in Rana esculenta skeletal muscle fibres. Previous papers had reported that skeletal muscle fibres exposed to a wide range of Extracellular sucrose concentrations resemble perfect osmometers with increased Extracellular Osmolarity proportionally decreasing fibre volume and therefore diminishing fibre radius, a. However, classical electrolyte theory (Robinson and Stokes 1959, Electrolyte solutions 2nd edn. Butterworth & Co. pp 41–42) would then predict that the consequent increases in intracellular ionic strength would correspondingly decrease sarcoplasmic resistivity, Ri. An extension of the original cable analysis then demonstrated that the latter would precisely offset its expected effect of alterations in a on the fibre axial resistance, ri, and leave action potential conduction velocity constant. In contrast, other reports (Hodgkin and Nakajima J Physiol 221:105–120, 1972) had suggested that Riincreased with Extracellular Osmolarity, owing to alterations in cytosolic viscosity. This led to a prediction of a decreased conduction velocity. These opposing hypotheses were then tested in muscle fibres subject to just-suprathreshold stimulation at a Vaseline seal at one end and measuring action potentials and their first order derivatives, dV/dt, using 5–20 MΩ, 3 M KCl glass microelectrodes at defined distances away from the stimulus sites. Exposures to hyperosmotic, sucrose-containing, Ringer solutions then reversibly reduced both conduction velocity and maximum values of dV/dt. This was compatible with an increase in Ri in the event that conduction depended upon a discharge of membrane capacitance by propagating local circuit currents through initially passive electrical elements. Conduction velocity then showed graded decreases with increasing Extracellular Osmolarity from 250–750 mOsm. Action potential waveforms through these Osmolarity changes remained similar, including both early surface and the late after-depolarisation events reflecting transverse tubular activation. Quantitative comparisons of reduced-χ 2 values derived from a comparison of these results and the differing predictions from the two hypotheses strongly favoured the hypothesis in which Riincreased rather than decreased with hyperOsmolarity. Electronic supplementary material The online version of this article (doi:10.1007/s10974-007-9115-8) contains supplementary material, which is available to authorized users.
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Conduction velocities in amphibian skeletal muscle fibres exposed to hyperosmotic Extracellular solutions
Journal of Muscle Research and Cell Motility, 2007Co-Authors: Zhongbo Chen, Sandeep S. Hothi, Wei Xu, Christopher L-h. HuangAbstract:Early quantitative analyses of conduction velocities in unmyelinated nerve studied in a constantly iso-osmotic volume conductor were extended to an analysis of the effects of varying Extracellular osmolarities on conduction velocities of surface membrane action potentials in Rana esculenta skeletal muscle fibres. Previous papers had reported that skeletal muscle fibres exposed to a wide range of Extracellular sucrose concentrations resemble perfect osmometers with increased Extracellular Osmolarity proportionally decreasing fibre volume and therefore diminishing fibre radius, a . However, classical electrolyte theory (Robinson and Stokes 1959, Electrolyte solutions 2nd edn. Butterworth & Co. pp 41–42) would then predict that the consequent increases in intracellular ionic strength would correspondingly decrease sarcoplasmic resistivity, R _ i . An extension of the original cable analysis then demonstrated that the latter would precisely offset its expected effect of alterations in a on the fibre axial resistance, r _ i , and leave action potential conduction velocity constant . In contrast, other reports (Hodgkin and Nakajima J Physiol 221:105–120, 1972) had suggested that R _ i increased with Extracellular Osmolarity, owing to alterations in cytosolic viscosity. This led to a prediction of a decreased conduction velocity. These opposing hypotheses were then tested in muscle fibres subject to just-suprathreshold stimulation at a Vaseline seal at one end and measuring action potentials and their first order derivatives, d V /d t , using 5–20 MΩ, 3 M KCl glass microelectrodes at defined distances away from the stimulus sites. Exposures to hyperosmotic, sucrose-containing, Ringer solutions then reversibly reduced both conduction velocity and maximum values of d V /d t . This was compatible with an increase in R _ i in the event that conduction depended upon a discharge of membrane capacitance by propagating local circuit currents through initially passive electrical elements. Conduction velocity then showed graded decreases with increasing Extracellular Osmolarity from 250–750 mOsm. Action potential waveforms through these Osmolarity changes remained similar, including both early surface and the late after-depolarisation events reflecting transverse tubular activation. Quantitative comparisons of reduced-χ ^2 values derived from a comparison of these results and the differing predictions from the two hypotheses strongly favoured the hypothesis in which R _ i increased rather than decreased with hyperOsmolarity.
