Role of voltage-dependent modulation of store Ca2+ release in synchronization of Ca2+ oscillations

Slow waves are rhythmic depolarizations that underlie mechanical activity of many smooth muscles. Slow waves result through rhythmic Ca2+ release from intracellular Ca2+ stores through inositol 1,4,5-trisphosphate (IP3) sensitive receptors and Ca2+-induced Ca2+ release. Ca2+ oscillations are transformed into membrane depolarizations by generation of a Ca2+-activated inward current. Importantly, the store Ca2+ oscillations that underlie slow waves are entrained across many cells over large distances. It has been shown that IP3 receptor-mediated Ca2+ release is enhanced by membrane depolarization. Previous studies have implicated diffusion of Ca2+ or the second messenger IP3 across gap junctions in synchronization of Ca2+ oscillations. In this study, a novel mechanism of Ca2+ store entrainment through depolarization- induced IP3 receptor-mediated Ca2+ release is investigated. This mechanism is signi. cantly different from chemical coupling- based mechanisms, as membrane potential has a coupling effect over distances several orders of magnitude greater than either diffusion of Ca2+ or IP3 through gap junctions. It is shown that electrical coupling acting through voltage-dependent modulation of store Ca2+ release is able to synchronize oscillations of cells even when cells are widely separated and have different intrinsic frequencies of oscillation.