Blink and You'll See It

Abstract

See related article, pages 210–218 Nearly 2 decades ago, local Ca2+ release events during diastole were first observed and named Ca2+ sparks.1 These were originally attributed to large releases from single ryanodine receptor (RyR) channels.1 Subsequently, Lipp and Niggli proposed that Ca2+ sparks could be the summation of smaller releases recruited from within the same cluster and coined the term calcium quarks.2 Arduous experiments from this group and others have indeed recorded very small release events proposed to be from smaller numbers of RyRs; however, such reports have remained limited.3,4 In this issue of Circulation Research , evidence is presented to show how small release events from within a RyR cluster are a key component of sarcoplasmic reticulum (SR) Ca2+ release.5 Physiologically, during depolarization, Ca2+ sparks are triggered throughout the cells by a small influx of Ca2+ from the sarcolemmal Ca2+ channels. The resultant synchronous rise in Ca2+ is observed as the systolic Ca2+ transient. This global Ca2+ release has been used to derive a measure of RyR function termed the “gain” of coupling between trigger Ca2+ influx and Ca2+ release. This yields a whole-cell measure of RyR function; changes in this gain infer changes in the RyR behavior, which may be attributable to several factors, including the SR Ca2+ load, or the sensitivity of the channels themselves (see Heinzel et al6 for review). As a more direct measure for RyR behavior, diastolic Ca2+ sparks have been characterized, in particular in studies of pathological conditions. Measurements of diastolic RyR behavior have been used to calculate loss of Ca2+ from the SR and how this would affect the SR Ca2+ load (eg, in Neef et al7 …