The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Anthony J. Ricci - One of the best experts on this subject based on the ideXlab platform.
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Calcium-Induced Calcium Release supports recruitment of synaptic vesicles in auditory hair cells
Journal of neurophysiology, 2015Co-Authors: Manuel Castellano-muñoz, Michael E. Schnee, Anthony J. RicciAbstract:Hair cells from auditory and vestibular systems transmit continuous sound and balance information to the central nervous system through the Release of synaptic vesicles at ribbon synapses. The high activity experienced by hair cells requires a unique mechanism to sustain recruitment and replenishment of synaptic vesicles for continuous Release. Using pre- and postsynaptic electrophysiological recordings, we explored the potential contribution of Calcium-Induced Calcium Release (CICR) in modulating the recruitment of vesicles to auditory hair cell ribbon synapses. Pharmacological manipulation of CICR with agents targeting endoplasmic reticulum Calcium stores reduced both spontaneous postsynaptic multiunit activity and the frequency of excitatory postsynaptic currents (EPSCs). Pharmacological treatments had no effect on hair cell resting potential or activation curves for Calcium and potassium channels. However, these drugs exerted a reduction in vesicle Release measured by dual-sine capacitance methods. In addition, Calcium substitution by barium reduced Release efficacy by delaying Release onset and diminishing vesicle recruitment. Together these results demonstrate a role for Calcium stores in hair cell ribbon synaptic transmission and suggest a novel contribution of CICR in hair cell vesicle recruitment. We hypothesize that Calcium entry via Calcium channels is tightly regulated to control timing of vesicle fusion at the synapse, whereas CICR is used to maintain a tonic Calcium signal to modulate vesicle trafficking.
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Role of intracellular Calcium stores in hair-cell ribbon synapse.
Frontiers in cellular neuroscience, 2014Co-Authors: Manuel Castellano-muñoz, Anthony J. RicciAbstract:Intracellular Calcium stores control many neuronal functions such as excitability, gene expression, synaptic plasticity, and synaptic Release. Although the existence of Calcium stores along with Calcium-Induced Calcium Release (CICR) has been demonstrated in conventional and ribbon synapses, functional significance and the cellular mechanisms underlying this role remains unclear. This review summarizes recent experimental evidence identifying contribution of CICR to synaptic transmission and synaptic plasticity in the CNS, retina and inner ear. In addition, the potential role of CICR in the recruitment of vesicles to releasable pools in hair-cell ribbon synapses will be specifically discussed.
Paulina Donoso - One of the best experts on this subject based on the ideXlab platform.
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Kinetic Studies of Calcium-Induced Calcium Release in Cardiac Sarcoplasmic Reticulum Vesicles
Biophysical journal, 2003Co-Authors: Gina Sánchez, Cecilia Hidalgo, Paulina DonosoAbstract:Fast Ca2+ Release kinetics were measured in cardiac sarcoplasmic reticulum vesicles actively loaded with Ca2+. Release was induced in solutions containing 1.2 mM free ATP and variable free [Ca2+] and [Mg2+]. Release rate constants (k) were 10-fold higher at pCa 6 than at pCa 5 whereas Ryanodine binding was highest at pCa ≤5. These results suggest that channels respond differently when exposed to sudden [Ca2+] changes than when exposed to Ca2+ for longer periods. Vesicles with severalfold different luminal Calcium contents exhibited double exponential Release kinetics at pCa 6, suggesting that channels undergo time-dependent activity changes. Addition of Mg2+ produced a marked inhibition of Release kinetics at pCa 6 (K0.5 = 63 μM) but not at pCa 5. Coexistence of Calcium activation and inhibition sites with equally fast binding kinetics is proposed to explain this behavior. Thimerosal activated Release kinetics at pCa 5 at all [Mg2+] tested and increased at pCa 6 the K0.5 for Mg2+ inhibition, from 63 μM to 136 μM. We discuss the possible relevance of these results, which suggest Release through RyR2 channels is subject to fast regulation by Ca2+ and Mg2+ followed by time-dependent regulation, to the physiological mechanisms of cardiac channel opening and closing.
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Sulfhydryl Oxidation Overrides Mg2+ Inhibition of Calcium-Induced Calcium Release in Skeletal Muscle Triads
Biophysical journal, 2000Co-Authors: Paulina Donoso, Paula Aracena, Cecilia HidalgoAbstract:We studied the effect of oxidation of sulfhydryl (SH) residues on the inhibition by Mg(2+) of Calcium-Induced Calcium Release (CICR) in triad-enriched sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle. Vesicles were either passively or actively loaded with Calcium before eliciting CICR by dilution at pCa 4.6-4.4 in the presence of 1.2 mM free [ATP] and variable free [Mg(2+)]. Native triads exhibited a significant inhibition of CICR by Mg(2+), with a K(0.5) approximately 50 microM. Partial oxidation of vesicles with thimerosal produced a significant increase of Release rate constants and initial Release rates at all [Mg(2+)] tested (up to 1 mM), and shifted the K(0.5) value for Mg(2+) inhibition to 101 or 137 microM in triads actively or passively loaded with Calcium, respectively. Further oxidation of vesicles with thimerosal completely suppressed the inhibitory effect of [Mg(2+)] on CICR, yielding initial rates of CICR of 2 micromol/(mg x s) in the presence of 1 mM free [Mg(2+)]. These effects of oxidation on CICR were fully reversed by SH reducing agents. We propose that oxidation of Calcium Release channels, by decreasing markedly the affinity of the channel inhibitory site for Mg(2+), makes CICR possible in skeletal muscle.
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Rapid Kinetic Studies of SH Oxidation-Induced Calcium Release from Sarcoplasmic Reticulum Vesicles
Archives of biochemistry and biophysics, 1997Co-Authors: Paulina Donoso, Patricia Rodrı́guez, Paola MarambioAbstract:Abstract We studied the kinetics of Calcium Release induced by SH oxidation in triads isolated from frog and rabbit skeletal muscle by measuring Calcium fluxes by a fast filtration method. In both species SH oxidation induced Release of 70–80% of the passively loaded Calcium with a rate constant of 1 s −1 . This rate constant is 3 times higher than the rate constant of Calcium-Induced Calcium Release and 15 times lower than the rate constant of ATP-induced Release. Calcium Release induced by SH oxidation exhibited the same Calcium dependence of Calcium-Induced Calcium Release and was also inhibited by physiological [Mg 2+ ]. Neither SH oxidation-induced Calcium Release nor Calcium-Induced Calcium Release were regulated by luminal Calcium. The redox state of thiol groups does not seem to control ATP-induced Calcium Release since the rate constant of Calcium Release after SH oxidation was not different from the rate constant measured in the presence of the reducing agent dithiothreitol. Our results do not support a role for SH oxidation, per se, as an essential step for the Release of Calcium from sarcoplasmic reticulum.
Wallace B. Thoreson - One of the best experts on this subject based on the ideXlab platform.
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Calcium-Induced Calcium Release contributes to synaptic Release from mouse rod photoreceptors
Neuroscience, 2009Co-Authors: Norbert Babai, Catherine W. Morgans, Wallace B. ThoresonAbstract:Abstract We tested whether Calcium-Induced Calcium Release (CICR) contributes to synaptic Release from rods in mammalian retina. Electron micrographs and immunofluorescent double labeling for the sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA2) and synaptic ribbon protein, ribeye, showed a close association between ER and synaptic ribbons in mouse rod terminals. Stimulating CICR with 10 μM ryanodine evoked Ca 2+ increases in rod terminals from mouse retinal slices visualized using confocal microscopy with the Ca 2+ -sensitive dye, Fluo-4. Ryanodine also stimulated membrane depolarization of individual mouse rods. Inhibiting CICR with a high concentration of ryanodine (100 μM) reduced the electroretinogram (ERG) b-wave but not a-wave consistent with inhibition of synaptic transmission from rods. Ryanodine (100 μM) also inhibited light-evoked voltage responses of individual rod bipolar cells (RBCs) and presumptive horizontal cells recorded with perforated patch recording techniques. A presynaptic site of action for ryanodine's effects is further indicated by the finding that ryanodine (100 μM) did not alter currents evoked in voltage-clamped RBCs by puffing the mGluR6 antagonist, (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG), onto bipolar cell dendrites in the presence of the mGluR6 agonist l -(+)-2-amino-4-phosphonobutyric acid ( l -AP4). Ryanodine (100 μM) also inhibited glutamatergic outward currents in RBCs evoked by electrical stimulation of rods using electrodes placed in the outer segment layer. Together, these results indicate that, like amphibian retina, CICR contributes to synaptic Release from mammalian (mouse) rods. By boosting synaptic Release in darkness, CICR may improve the detection of small luminance changes by post-synaptic neurons.
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Calcium-Induced Calcium Release in rod photoreceptor terminals boosts synaptic transmission during maintained depolarization.
The European journal of neuroscience, 2006Co-Authors: Lucia Cadetti, Eric J. Bryson, Cory A. Ciccone, Katalin Rabl, Wallace B. ThoresonAbstract:We examined the contribution of Calcium-Induced Calcium Release (CICR) to synaptic transmission from rod photoreceptor terminals. Whole-cell recording and confocal Calcium imaging experiments were conducted on rods with intact synaptic terminals in a retinal slice preparation from salamander. Low concentrations of ryanodine stimulated Calcium increases in rod terminals, consistent with the presence of ryanodine receptors. Application of strong depolarizing steps (-70 to -10 mV) exceeding 200 ms or longer in duration evoked a wave of Calcium that spread across the synaptic terminals of voltage-clamped rods. This secondary Calcium increase was blocked by high concentrations of ryanodine, indicating it was due to CICR. Ryanodine (50 microm) had no significant effect on rod Calcium current (I(ca)) although it slightly diminished rod light-evoked voltage responses. Bath application of 50 microm ryanodine strongly inhibited light-evoked currents in horizontal cells. Whether applied extracellularly or delivered into the rod cell through the patch pipette, ryanodine (50 microm) also inhibited excitatory post-synaptic currents (EPSCs) evoked in horizontal cells by depolarizing steps applied to rods. Ryanodine caused a preferential reduction in the later portions of EPSCs evoked by depolarizing steps of 200 ms or longer. These results indicate that CICR enhances Calcium increases in rod terminals evoked by sustained depolarization, which in turn acts to boost synaptic exocytosis from rods.
Manuel Castellano-muñoz - One of the best experts on this subject based on the ideXlab platform.
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Calcium-Induced Calcium Release supports recruitment of synaptic vesicles in auditory hair cells
Journal of neurophysiology, 2015Co-Authors: Manuel Castellano-muñoz, Michael E. Schnee, Anthony J. RicciAbstract:Hair cells from auditory and vestibular systems transmit continuous sound and balance information to the central nervous system through the Release of synaptic vesicles at ribbon synapses. The high activity experienced by hair cells requires a unique mechanism to sustain recruitment and replenishment of synaptic vesicles for continuous Release. Using pre- and postsynaptic electrophysiological recordings, we explored the potential contribution of Calcium-Induced Calcium Release (CICR) in modulating the recruitment of vesicles to auditory hair cell ribbon synapses. Pharmacological manipulation of CICR with agents targeting endoplasmic reticulum Calcium stores reduced both spontaneous postsynaptic multiunit activity and the frequency of excitatory postsynaptic currents (EPSCs). Pharmacological treatments had no effect on hair cell resting potential or activation curves for Calcium and potassium channels. However, these drugs exerted a reduction in vesicle Release measured by dual-sine capacitance methods. In addition, Calcium substitution by barium reduced Release efficacy by delaying Release onset and diminishing vesicle recruitment. Together these results demonstrate a role for Calcium stores in hair cell ribbon synaptic transmission and suggest a novel contribution of CICR in hair cell vesicle recruitment. We hypothesize that Calcium entry via Calcium channels is tightly regulated to control timing of vesicle fusion at the synapse, whereas CICR is used to maintain a tonic Calcium signal to modulate vesicle trafficking.
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Role of intracellular Calcium stores in hair-cell ribbon synapse.
Frontiers in cellular neuroscience, 2014Co-Authors: Manuel Castellano-muñoz, Anthony J. RicciAbstract:Intracellular Calcium stores control many neuronal functions such as excitability, gene expression, synaptic plasticity, and synaptic Release. Although the existence of Calcium stores along with Calcium-Induced Calcium Release (CICR) has been demonstrated in conventional and ribbon synapses, functional significance and the cellular mechanisms underlying this role remains unclear. This review summarizes recent experimental evidence identifying contribution of CICR to synaptic transmission and synaptic plasticity in the CNS, retina and inner ear. In addition, the potential role of CICR in the recruitment of vesicles to releasable pools in hair-cell ribbon synapses will be specifically discussed.
Michael I. Kotlikoff - One of the best experts on this subject based on the ideXlab platform.
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Calcium-Induced Calcium Release in smooth muscle: the case for loose coupling.
Progress in biophysics and molecular biology, 2003Co-Authors: Michael I. KotlikoffAbstract:Abstract This article reviews the key experiments demonstrating Calcium-Induced Calcium Release (CICR) in smooth muscle and contrasts the biophysical and molecular features of coupling between the sarcolemmal (L-type Ca 2+ channel) and sarcoplasmic reticulum (ryanodine receptor) Ca 2+ channels in smooth and cardiac muscle. Loose coupling refers to the coupling process in smooth muscle in which gating of ryanodine receptors is non-obligate and may occur with a variable delay following opening of the sarcolemmal Ca 2+ channels. These features have been observed in the earliest studies of CICR in smooth muscle and are in marked contrast to cardiac CICR, where a close coupling between T-tubular and SR membranes results in tight coupling between the gating events. The relationship between this “loose coupling” and distinct subcellular Release sites within smooth muscle cells, termed frequent discharge sites, is discussed.
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Calcium-Induced Calcium Release in smooth muscle: loose coupling between the action potential and Calcium Release.
The Journal of general physiology, 2000Co-Authors: Mei Lin Collier, Y. X. Wang, Michael I. KotlikoffAbstract:Calcium-Induced Calcium Release (CICR) has been observed in cardiac myocytes as elementary Calcium Release events (Calcium sparks) associated with the opening of L-type Ca2+ channels. In heart cells, a tight coupling between the gating of single L-type Ca2+ channels and ryanodine receptors (RYRs) underlies Calcium Release. Here we demonstrate that L-type Ca2+ channels activate RYRs to produce CICR in smooth muscle cells in the form of Ca2+ sparks and propagated Ca2+ waves. However, unlike CICR in cardiac muscle, RYR channel opening is not tightly linked to the gating of L-type Ca2+ channels. L-type Ca2+ channels can open without triggering Ca2+ sparks and triggered Ca2+ sparks are often observed after channel closure. CICR is a function of the net flux of Ca2+ ions into the cytosol, rather than the single channel amplitude of L-type Ca2+ channels. Moreover, unlike CICR in striated muscle, Calcium Release is completely eliminated by cytosolic Calcium buffering. Thus, L-type Ca2+ channels are loosely coupled to RYR through an increase in global [Ca2+] due to an increase in the effective distance between L-type Ca2+ channels and RYR, resulting in an uncoupling of the obligate relationship that exists in striated muscle between the action potential and Calcium Release.
