ryanodine 受体开放时间由关闭状态决定。
Ryanodine Receptor Open Times Are Determined in the Closed State.
机构信息
Department of Physiology and Biophysics, Rush University Medical Center, Chicago, Illinois.
Department of Physiology and Biophysics, Rush University Medical Center, Chicago, Illinois.
出版信息
Biophys J. 2018 Oct 2;115(7):1160-1165. doi: 10.1016/j.bpj.2018.08.025. Epub 2018 Sep 13.
Abstract
The ryanodine receptor (RyR) ion channel releases Ca from intracellular stores by conducting Ca but also by recruiting neighboring RyRs to open, as RyRs are activated by micromolar levels of cytosolic Ca. Using long single-RyR recordings of the cardiac isoform (RyR2), we conclude that Ca binding to the cytosolic face of RyR while the channel is closed determines the distribution of open times. This mechanism explains previous findings that RyR is not activated by its own fluxed Ca. Our measurements also bolster previous findings that luminal [Ca] can affect both the cytosolic activation and inactivation sites and that RyR has different gating modes for the same ionic conditions.
摘要
ryanodine 受体 (RyR) 离子通道通过传导 Ca 来释放细胞内储存的 Ca，还可以通过招募相邻的 RyR 来打开，因为 RyR 被细胞浆内 Ca 浓度的微摩尔水平激活。使用心脏同工型 (RyR2) 的长单个 RyR 记录，我们得出结论，当通道关闭时，Ca 与 RyR 的细胞浆面结合决定了开放时间的分布。这种机制解释了先前的发现，即 RyR 不会被其自身的钙流激活。我们的测量结果也支持了先前的发现，即腔 [Ca] 可以影响细胞浆激活和失活部位，并且 RyR 在相同的离子条件下具有不同的门控模式。
相似文献
1
Ryanodine Receptor Open Times Are Determined in the Closed State.
Biophys J. 2018 Oct 2;115(7):1160-1165. doi: 10.1016/j.bpj.2018.08.025. Epub 2018 Sep 13.
2
Recruiting RyRs to Open in a Ca Release Unit: Single-RyR Gating Properties Make RyR Group Dynamics.
Biophys J. 2020 Jan 7;118(1):232-242. doi: 10.1016/j.bpj.2019.11.021. Epub 2019 Nov 23.
3
Modification of ryanodine receptor/Ca2+ release channel with dinitrofluorobenzene.
Biochem J. 1999 Aug 15;342 ( Pt 1)(Pt 1):239-48. doi: 10.1042/0264-6021:3420239.
4
The role of calsequestrin, triadin, and junctin in conferring cardiac ryanodine receptor responsiveness to luminal calcium.
Biophys J. 2004 Apr;86(4):2121-8. doi: 10.1016/S0006-3495(04)74271-X.
5
Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites.
Clin Exp Pharmacol Physiol. 2007 Sep;34(9):889-96. doi: 10.1111/j.1440-1681.2007.04708.x.
6
Coupled gating modifies the regulation of cardiac ryanodine receptors by luminal Ca(2+).
Biochim Biophys Acta. 2014 Mar;1838(3):867-73. doi: 10.1016/j.bbamem.2013.11.005. Epub 2013 Nov 14.
7
Molecular Insights into Calcium Dependent Regulation of Ryanodine Receptor Calcium Release Channels.
Adv Exp Med Biol. 2020;1131:321-336. doi: 10.1007/978-3-030-12457-1_13.
8
The unliganded long isoform of estrogen receptor beta stimulates brain ryanodine receptor single channel activity alongside with cytosolic Ca2+.
J Recept Signal Transduct Res. 2009 Dec;29(6):326-41. doi: 10.3109/10799890903295168.
9
Characterization of a calcium-regulation domain of the skeletal-muscle ryanodine receptor.
Biochem J. 2000 Oct 1;351(Pt 1):57-65. doi: 10.1042/0264-6021:3510057.
10
Luminal Ca(2+) activation of cardiac ryanodine receptors by luminal and cytoplasmic domains.
Eur Biophys J. 2009 Dec;39(1):19-26. doi: 10.1007/s00249-009-0417-1. Epub 2009 Mar 3.
引用本文的文献
1
Blink nadir measurements of sarcoplasmic reticulum are consistent with strong local Ca depletion.
Biophys J. 2025 Jan 21;124(2):245-255. doi: 10.1016/j.bpj.2024.11.3316. Epub 2024 Nov 27.
2
Ca spark latency and control of intrinsic Ca release dyssynchrony in rat cardiac ventricular muscle cells.
J Mol Cell Cardiol. 2023 Sep;182:44-53. doi: 10.1016/j.yjmcc.2023.07.005. Epub 2023 Jul 9.
3
The Role of Ca Sparks in Force Frequency Relationships in Guinea Pig Ventricular Myocytes.
Biomolecules. 2022 Oct 27;12(11):1577. doi: 10.3390/biom12111577.
4
The role of subunit cooperativity on ryanodine receptor 2 calcium signaling.
Biophys J. 2023 Jan 3;122(1):215-229. doi: 10.1016/j.bpj.2022.11.008. Epub 2022 Nov 7.
5
Mechanisms of spontaneous Ca release-mediated arrhythmia in a novel 3D human atrial myocyte model: I. Transverse-axial tubule variation.
J Physiol. 2023 Jul;601(13):2655-2683. doi: 10.1113/JP283363. Epub 2022 Oct 27.
6
Image-Driven Modeling of Nanoscopic Cardiac Function: Where Have We Come From, and Where Are We Going?
Front Physiol. 2022 Mar 8;13:834211. doi: 10.3389/fphys.2022.834211. eCollection 2022.
7
Flecainide Paradoxically Activates Cardiac Ryanodine Receptor Channels under Low Activity Conditions: A Potential Pro-Arrhythmic Action.
Cells. 2021 Aug 16;10(8):2101. doi: 10.3390/cells10082101.
8
Cardiomyocyte Calcium Ion Oscillations-Lessons From Physics.
Front Physiol. 2020 Feb 28;11:164. doi: 10.3389/fphys.2020.00164. eCollection 2020.
9
Recruiting RyRs to Open in a Ca Release Unit: Single-RyR Gating Properties Make RyR Group Dynamics.
Biophys J. 2020 Jan 7;118(1):232-242. doi: 10.1016/j.bpj.2019.11.021. Epub 2019 Nov 23.
本文引用的文献
1
The cardiac ryanodine receptor luminal Ca2+ sensor governs Ca2+ waves, ventricular tachyarrhythmias and cardiac hypertrophy in calsequestrin-null mice.
Biochem J. 2014 Jul 1;461(1):99-106. doi: 10.1042/BJ20140126.
2
Mechanism of calsequestrin regulation of single cardiac ryanodine receptor in normal and pathological conditions.
J Gen Physiol. 2013 Aug;142(2):127-36. doi: 10.1085/jgp.201311022. Epub 2013 Jul 15.
3
On Brownian Distance Covariance and High Dimensional Data.
Ann Appl Stat. 2009 Jan 1;3(4):1266-1269. doi: 10.1214/09-AOAS312.
4
Flux regulation of cardiac ryanodine receptor channels.
J Gen Physiol. 2010 Jan;135(1):15-27. doi: 10.1085/jgp.200910273. Epub 2009 Dec 14.
5
Luminal Mg2+, a key factor controlling RYR2-mediated Ca2+ release: cytoplasmic and luminal regulation modeled in a tetrameric channel.
J Gen Physiol. 2008 Oct;132(4):429-46. doi: 10.1085/jgp.200810001.
6
Luminal Ca2+ regulation of single cardiac ryanodine receptors: insights provided by calsequestrin and its mutants.
J Gen Physiol. 2008 Apr;131(4):325-34. doi: 10.1085/jgp.200709907. Epub 2008 Mar 17.
7
Energetics of divalent selectivity in a calcium channel: the ryanodine receptor case study.
Biophys J. 2008 Feb 15;94(4):1169-84. doi: 10.1529/biophysj.107.116798. Epub 2007 Oct 19.
8
Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites.
Biophys J. 2007 May 15;92(10):3541-55. doi: 10.1529/biophysj.106.099028. Epub 2007 Mar 9.
9
Comparison of the effects exerted by luminal Ca2+ on the sensitivity of the cardiac ryanodine receptor to caffeine and cytosolic Ca2+.
J Membr Biol. 2006;212(1):17-28. doi: 10.1007/s00232-006-7018-z. Epub 2007 Jan 6.
10
Regulation of ryanodine receptors by calsequestrin: effect of high luminal Ca2+ and phosphorylation.
Biophys J. 2005 May;88(5):3444-54. doi: 10.1529/biophysj.104.051441. Epub 2005 Feb 24.
Zotero 插件