Synchronization of Ca2+ oscillations: a coupled oscillator-based mechanism in smooth muscle

Entrained oscillations in Ca(2+) underlie many biological pacemaking phenomena. In this article, we review a long-range signaling mechanism in smooth muscle that results in global outcomes of local interactions. Our results are derived from studies of the following: (a) slow-wave depolarizations that underlie rhythmic contractions of gastric smooth muscle; and (b) membrane depolarizations that drive rhythmic contractions of lymphatic smooth muscle. The main feature of this signaling mechanism is a coupled oscillator-based synchronization of Ca(2+) oscillations across cells that drives membrane potential changes and causes coordinated contractions. The key elements of this mechanism are as follows: (a) the Ca(2+) release-refill cycle of endoplasmic reticulum Ca(2+) stores; (b) Ca(2+)-dependent modulation of membrane currents; (c) voltage-dependent modulation of Ca(2+) store release; and (d) cell-cell coupling through gap junctions or other mechanisms. In this mechanism, Ca(2+) stores alter the frequency of adjacent stores through voltage-dependent modulation of store release. This electrochemical coupling is many orders of magnitude stronger than the coupling through diffusion of Ca(2+) or inositol 1,4,5-trisphosphate, and thus provides an effective means of long-range signaling.