Ca²⁺ Spark as a Regulator of Ion Channel Activity

Abstract

Ca²⁺ spark is a local and transient Ca²⁺ release from sarcoplasmic reticulum (SR) through the ryanodine receptor Ca²⁺-releasing channel (RyR). In cardiac myocytes, Ca²⁺ spark is an elementary unit of Ca²⁺-induced Ca²⁺ release (CICR) by opening of RyR(s) in junctional SR (jSR), which is triggered by Ca²⁺-influx through L-type Ca²⁺ channels to the narrow space between a transverse tubule and jSR. Ca²⁺ spark has, therefore, been described as the evidence for “the local control of excitation-contraction coupling”. In contrast, Ca²⁺ sparks in smooth muscle have been reported in relation to Ca²⁺-dependent K⁺ (K_Ca) channel activation and muscle relaxation. A spontaneous Ca²⁺ spark in a superficial area activates 10 - 100 K_Ca channels nearby and induces membrane hyperpolarization, which reduces Ca²⁺ channel activity. In several types of smooth muscle cells, which have relatively high membrane excitability, an action potential (AP) elicits 5 - 20 Ca²⁺ hot spots (evoked sparks with long life) in the early stage via CICR in discrete superficial SR elements and activates K_Ca-channel current highly responsible for AP repolarization and afterhyperpolarization. CICR available for contraction may occur more slowly by the propagation of CICR from superficial SR to deeper ones. The regulatory mechanism of ion channel activity on plasma membrane by superficial SR via Ca²⁺ spark generation in smooth muscle cells may be analogously common in several types of cells including neurons.