Figure 2.

STOC-mediated vasodilation mechanism. In vascular smooth muscle, BK channels are key drivers of negative feedback control via the regulation of membrane excitability, an essential mechanism that prevents excessive constriction of resistance arteries (1). Specifically, transient activation of ryanodine receptors (RyR) residing in the sarcoplasmic reticulum leads to the generation of “Ca²⁺ sparks” (2). Single sparks increase the Ca²⁺ concentration in the vicinity of membrane BK channels, provoking their opening and the subsequent development of macroscopic K⁺ currents referred to as “Spontaneous transient outward currents (STOCs)” (3). This in turn, contributes to membrane hyperpolarization by reducing the voltage-gated Ca²⁺ channel (VGCC) open probability (4), and a relative reduction in the intracellular Ca²⁺ levels (5). As a result, the resistance artery develops a dilatory response (6), a vital feedback mechanism to optimize arterial tone development (Nelson et al., 1995).