Small Ca 2+ Release Events in Rabbit Ventricular Myocytes

Abstract

The cell-wide Ca2+ release that occurs during excitation-contraction coupling in heart is thought to arise from the synchronized activation of many elementary calcium release events, Ca2+ sparks. Using cytosolic Ca2+ sensitive fluorescent indicators like fluo-4, Ca2+ sparks have been visualized in diverse tissues (muscles, neurons and even non-excitable cells) and species (rat, mouse, rabbit, dog, cat and human). During the time when Ca2+ is being released from the sarcoplasmic reticulum (SR) in heart during a single Ca2+ sparks, a reciprocal Ca2+ depletion is occurring in the SR and this can be visualized with low affinity Ca2+ indicators like fluo-5N loaded into the SR. Such events, known as Ca2+ blinks, can be measured and they reveal the depletion signal with high temporal (milliseconds) and spatial resolution (Brochet et al., PNAS, 2005) and thus reveal information on the inner workings of the SR. The SR organelle must be in excellent optical focus when Ca2+ sparks and Ca2+ blinks are obtained simultaneously and has enabled us to visualize a population of Ca2+ release events that are smaller than Ca2+ sparks. These “sub-spark” Ca2+ release events have been named ‘quarky’ Ca2+ release events. Here we report on such events that may occur over both a limited and an extensive area (across several sarcomeres). The mechanisms whereby local and extensive quarky Ca2+ release events may occur will be discussed. The existence of such quarky Ca2+ release co-mingled with the more prominent Ca2+ spark based Ca2+ release provides important new understanding of cardiac Ca2+ signaling in health and disease.