PNAS — Termination of Ca 2+ release by a local inactivation of ryanodine receptors in cardiac myocytes Export

@article{citeulike:2961521, abstract = {ABSTRACT In heart, a robust regulatory mechanism is required to counteract the regenerative Ca21-induced Ca21 release from the sarcoplasmic reticulum. Several mechanisms, including inactivation, adaptation, and stochastic closing of ryanodine receptors (RyRs) have been proposed, but no conclusive evidence has yet been provided. We probed the termination process of Ca21 release by using a technique of imaging local Ca21 release, or ''Ca21 spikes'', at subcellular sites; and we tracked the kinetics of Ca21 release triggered by L-type Ca21 channels. At 0 mV, Ca21 release occurred and terminated within 40 ms after the onset of clamp pulses (0 mV). Increasing the open-duration and promoting the reopenings of Ca21 channels with the Ca21 channel agonist, FPL64176, did not prolong or trigger secondary Ca21 spikes, even though two-thirds of the sarcoplasmic reticulum Ca21 remained available for release. Latency of Ca21 spikes coincided with the first openings but not with the reopenings of L-type Ca21 channels. After an initial maximal release, even a multi-fold increase in unitary Ca21 current induced by a hyperpolarization to 2120 mV failed to trigger additional release, indicating absolute refractoriness of RyRs. When the release was submaximal (e.g., at 130 mV), tail currents did activate additional Ca21 spikes; confocal images revealed that they originated from RyRs unfired during depolarization. These results indicate that Ca21 release is terminated primarily by a highly localized, use-dependent inactivation of RyRs but not by the stochastic closing or adaptation of RyRs in intact ventricular myocytes.}, author = {Sham and Song, Long-Sheng and Chen, Ye and Deng, Li-Hua and Stern, Michael D. and Lakatta, Edward G. and Cheng, Heping}, citeulike-article-id = {2961521}, citeulike-linkout-0 = {http://www.pnas.org/content/95/25/15096.abstract}, journal = {PNAS}, keywords = {bapta, ca-spikes, cicr-termination, dhpr, egta, fpl, oregon-green-488, rat, refractoriness, ryr-inactivation, tail-current, ventricular-myocytes}, number = {25}, pages = {15096--15101}, posted-at = {2008-07-04 01:14:32}, priority = {2}, title = {PNAS — Termination of Ca 2+ release by a local inactivation of ryanodine receptors in cardiac myocytes}, url = {http://www.pnas.org/content/95/25/15096.abstract}, volume = {95}, year = {1998} }

TY - JOUR ID - citeulike:2961521 L3 - citeulike-article-id:2961521 N2 - ABSTRACT In heart, a robust regulatory mechanism is required to counteract the regenerative Ca21-induced Ca21 release from the sarcoplasmic reticulum. Several mechanisms, including inactivation, adaptation, and stochastic closing of ryanodine receptors (RyRs) have been proposed, but no conclusive evidence has yet been provided. We probed the termination process of Ca21 release by using a technique of imaging local Ca21 release, or ‘‘Ca21 spikes’’, at subcellular sites; and we tracked the kinetics of Ca21 release triggered by L-type Ca21 channels. At 0 mV, Ca21 release occurred and terminated within 40 ms after the onset of clamp pulses (0 mV). Increasing the open-duration and promoting the reopenings of Ca21 channels with the Ca21 channel agonist, FPL64176, did not prolong or trigger secondary Ca21 spikes, even though two-thirds of the sarcoplasmic reticulum Ca21 remained available for release. Latency of Ca21 spikes coincided with the first openings but not with the reopenings of L-type Ca21 channels. After an initial maximal release, even a multi-fold increase in unitary Ca21 current induced by a hyperpolarization to 2120 mV failed to trigger additional release, indicating absolute refractoriness of RyRs. When the release was submaximal (e.g., at 130 mV), tail currents did activate additional Ca21 spikes; confocal images revealed that they originated from RyRs unfired during depolarization. These results indicate that Ca21 release is terminated primarily by a highly localized, use-dependent inactivation of RyRs but not by the stochastic closing or adaptation of RyRs in intact ventricular myocytes. IS - 25 JF - PNAS EP - 15101 TI - PNAS — Termination of Ca 2+ release by a local inactivation of ryanodine receptors in cardiac myocytes VL - 95 SP - 15096 KW - bapta KW - ca-spikes KW - cicr-termination KW - dhpr KW - egta KW - fpl KW - oregon-green-488 KW - rat KW - refractoriness KW - ryr-inactivation KW - tail-current KW - ventricular-myocytes AU - Sham AU - Song, Long-Sheng AU - Chen, Ye AU - Deng, Li-Hua AU - Stern, Michael AU - Lakatta, Edward AU - Cheng, Heping PY - 1998/// UR - http://www.pnas.org/content/95/25/15096.abstract ER -