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 Ca^sup 2+^ release from intracellular Ca^sup 2+^ stores through inositol 1,4,5-trisphosphate (IP^sub 3^) sensitive receptors and Ca^sup 2+^-induced Ca^sup 2+^ release. Ca^sup 2+^ oscillations are transformed into membrane depolarizations by generation of a Ca^sup 2+^-activated inward current. Importantly, the store Ca^sup 2+^ oscillations that underlie slow waves are entrained across many cells over large distances. It has been shown that IP^sub 3^ receptor-mediated Ca^sup 2+^ release is enhanced by membrane depolarization. Previous studies have implicated diffusion of Ca^sup 2+^ or the second messenger IP^sub 3^ across gap junctions in synchronization of Ca^sup 2+^ oscillations. In this study, a novel mechanism of Ca^sup 2+^ store entrainment through depolarization-induced IP^sub 3^ receptor-mediated Ca^sup 2+^ release is investigated. This mechanism is significantly different from chemical coupling-based mechanisms, as membrane potential has a coupling effect over distances several orders of magnitude greater than either diffusion of Ca^sup 2+^ or IP^sub 3^ through gap junctions. It is shown that electrical coupling acting through voltage-dependent modulation of store Ca^sup 2+^ release is able to synchronize oscillations of cells even when cells are widely separated and have different intrinsic frequencies of oscillation.