Ryanodine Receptor Open Times Are Determined in the Closed State

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2018 Sep 18

PMID 30220413

Citations 8

Authors

Michael Fill

Dirk Gillespie

Affiliations

Soon will be listed here.

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.

Citing Articles

Blink nadir measurements of sarcoplasmic reticulum are consistent with strong local Ca depletion.

Gillespie D Biophys J. 2024; 124(2):245-255.

PMID: 39604260 PMC: 11788478. DOI: 10.1016/j.bpj.2024.11.3316.

Ca spark latency and control of intrinsic Ca release dyssynchrony in rat cardiac ventricular muscle cells.

Kong C, Cannell M J Mol Cell Cardiol. 2023; 182:44-53.

PMID: 37433391 PMC: 7616665. DOI: 10.1016/j.yjmcc.2023.07.005.

The Role of Ca Sparks in Force Frequency Relationships in Guinea Pig Ventricular Myocytes.

Paudel R, Jafri M, Ullah A Biomolecules. 2022; 12(11).

PMID: 36358926 PMC: 9687237. DOI: 10.3390/biom12111577.

The role of subunit cooperativity on ryanodine receptor 2 calcium signaling.

Greene D, Luchko T, Shiferaw Y Biophys J. 2022; 122(1):215-229.

PMID: 36348625 PMC: 9822801. DOI: 10.1016/j.bpj.2022.11.008.

Mechanisms of spontaneous Ca release-mediated arrhythmia in a novel 3D human atrial myocyte model: I. Transverse-axial tubule variation.

Zhang X, Ni H, Morotti S, Smith C, Sato D, Louch W J Physiol. 2022; 601(13):2655-2683.

PMID: 36094888 PMC: 10008525. DOI: 10.1113/JP283363.

References

Saftenku E, Williams A, Sitsapesan R . Markovian models of low and high activity levels of cardiac ryanodine receptors. Biophys J. 2001; 80(6):2727-41. PMC: 1301459. DOI: 10.1016/S0006-3495(01)76241-8. View

Rosales R, Fill M, Escobar A . Calcium regulation of single ryanodine receptor channel gating analyzed using HMM/MCMC statistical methods. J Gen Physiol. 2004; 123(5):533-53. PMC: 2234502. DOI: 10.1085/jgp.200308868. View

Tu Q, Velez P, BRODWICK M, Fill M . Streaming potentials reveal a short ryanodine-sensitive selectivity filter in cardiac Ca2+ release channel. Biophys J. 1994; 67(6):2280-5. PMC: 1225612. DOI: 10.1016/S0006-3495(94)80713-1. View

Laver D . Ca2+ stores regulate ryanodine receptor Ca2+ release channels via luminal and cytosolic Ca2+ sites. Biophys J. 2007; 92(10):3541-55. PMC: 1853142. DOI: 10.1529/biophysj.106.099028. View

Kosorok M . On Brownian Distance Covariance and High Dimensional Data. Ann Appl Stat. 2010; 3(4):1266-1269. PMC: 2889501. DOI: 10.1214/09-AOAS312. View

Sitsapesan R, Williams A . Gating of the native and purified cardiac SR Ca(2+)-release channel with monovalent cations as permeant species. Biophys J. 1994; 67(4):1484-94. PMC: 1225511. DOI: 10.1016/S0006-3495(94)80622-8. View

Chen H, Valle G, Furlan S, Nani A, Gyorke S, Fill M . Mechanism of calsequestrin regulation of single cardiac ryanodine receptor in normal and pathological conditions. J Gen Physiol. 2013; 142(2):127-36. PMC: 3727306. DOI: 10.1085/jgp.201311022. View

Qin J, Valle G, Nani A, Nori A, Rizzi N, Priori S . Luminal Ca2+ regulation of single cardiac ryanodine receptors: insights provided by calsequestrin and its mutants. J Gen Physiol. 2008; 131(4):325-34. PMC: 2279168. DOI: 10.1085/jgp.200709907. View

Gaburjakova J, Gaburjakova M . Comparison of the effects exerted by luminal Ca2+ on the sensitivity of the cardiac ryanodine receptor to caffeine and cytosolic Ca2+. J Membr Biol. 2007; 212(1):17-28. DOI: 10.1007/s00232-006-7018-z. View

10.

Laver D, Honen B . Luminal Mg2+, a key factor controlling RYR2-mediated Ca2+ release: cytoplasmic and luminal regulation modeled in a tetrameric channel. J Gen Physiol. 2008; 132(4):429-46. PMC: 2553390. DOI: 10.1085/jgp.200810001. View

11.

Gillespie D . Energetics of divalent selectivity in a calcium channel: the ryanodine receptor case study. Biophys J. 2007; 94(4):1169-84. PMC: 2212702. DOI: 10.1529/biophysj.107.116798. View

12.

Chamberlain B, Fleischer S . Isolation of canine cardiac sarcoplasmic reticulum. Methods Enzymol. 1988; 157:91-9. DOI: 10.1016/0076-6879(88)57071-4. View

13.

Liu Y, Porta M, Qin J, Ramos J, Nani A, R Shannon T . Flux regulation of cardiac ryanodine receptor channels. J Gen Physiol. 2009; 135(1):15-27. PMC: 2806413. DOI: 10.1085/jgp.200910273. View

14.

Zahradnikova A, Dura M, Gyorke S . Modal gating transitions in cardiac ryanodine receptors during increases of Ca2+ concentration produced by photolysis of caged Ca2+. Pflugers Arch. 1999; 438(3):283-8. DOI: 10.1007/s004240050911. View

15.

Sigworth F, Sine S . Data transformations for improved display and fitting of single-channel dwell time histograms. Biophys J. 1987; 52(6):1047-54. PMC: 1330104. DOI: 10.1016/S0006-3495(87)83298-8. View

16.

Xu L, Meissner G . Regulation of cardiac muscle Ca2+ release channel by sarcoplasmic reticulum lumenal Ca2+. Biophys J. 1998; 75(5):2302-12. PMC: 1299904. DOI: 10.1016/S0006-3495(98)77674-X. View

17.

Beard N, Casarotto M, Wei L, Varsanyi M, Laver D, Dulhunty A . Regulation of ryanodine receptors by calsequestrin: effect of high luminal Ca2+ and phosphorylation. Biophys J. 2005; 88(5):3444-54. PMC: 1305491. DOI: 10.1529/biophysj.104.051441. View

18.

Gyorke I, Hester N, Jones L, Gyorke S . The role of calsequestrin, triadin, and junctin in conferring cardiac ryanodine receptor responsiveness to luminal calcium. Biophys J. 2004; 86(4):2121-8. PMC: 1304063. DOI: 10.1016/S0006-3495(04)74271-X. View

19.

Stern M . Buffering of calcium in the vicinity of a channel pore. Cell Calcium. 1992; 13(3):183-92. DOI: 10.1016/0143-4160(92)90046-u. View

20.

Zahradnikova A, Zahradnik I . Description of modal gating of the cardiac calcium release channel in planar lipid membranes. Biophys J. 1995; 69(5):1780-8. PMC: 1236411. DOI: 10.1016/S0006-3495(95)80048-2. View