Ryanodine receptor adaptation

Authors

Michael Fill
A. Zahradníková
Carlos A. Villalba-Galea, Texas Tech University Health Sciences CenterFollow
I. Zahradník
A. L. Escobar
S. Györke

ORCiD

0000-0002-6489-4651

Document Type

Article

Publication Title

The Journal of General Physiology

ISSN

1540-7748

Volume

116

Issue

6

DOI

10.1085/jgp.116.6.873

First Page

873

Last Page

882

Publication Date

12-1-2000

Abstract

In the heart, depolarization during the action potential activates voltage-dependent Ca²⁺ channels that mediate a small, localized Ca²⁺ influx (I_Ca). This small Ca²⁺ signal activates specialized Ca²⁺ release channels, the ryanodine receptors (RyRs), in the sarcoplasmic reticulum (SR). This process is called Ca²⁺-induced Ca²⁺ release (CICR). Intuitively, the CICR process should be self-regenerating because the Ca²⁺ released from the SR should feedback and activate further SR Ca²⁺ release. However, the CICR process is precisely controlled in the heart and, consequently, some sort of negative control mechanism(s) must exist to counter the inherent positive feedback of the CICR process. Defining the nature of this negative control has been a focus of investigation for decades. Several mechanisms have been suggested including all of the following: Ca²⁺-dependent inactivation, adaptation, stochastic attrition, “fateful” inactivation, SR Ca²⁺ depletion, and coupled RyR gating. These mechanisms are generally regarded as being mutually exclusive (i.e., alternative). An emerging and more sophisticated view is that the required negative control is probably provided by a synergy of mechanisms, not a single mechanism.

In this perspective, we focus on the origin of Ca²⁺-dependent inactivation and adaptation of single cardiac RyR channels. Specific concerns about the adaptation phenomenon are addressed and a comprehensive unifying view of RyR Ca²⁺ regulation is forwarded. We conclude that the steady-state Ca²⁺ dependence, high Ca²⁺ inactivation and low Ca²⁺ adaptation are three distinct manifestations of the same underlying mechanism, Ca²⁺-dependent modal RyR channel gating.

Comments

Authors retain copyright

Recommended Citation

Fill, M., Zahradníková, A., Villalba-Galea, C. A., Zahradník, I., Escobar, A. L., & Györke, S. (2000). Ryanodine receptor adaptation. The Journal of General Physiology, 116(6), 873–882. DOI: 10.1085/jgp.116.6.873
https://scholarlycommons.pacific.edu/phs-facarticles/302

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