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

¹ The University of Newcastle, Australia
² The University of Southern Florida, USA
³ The University of Melbourne, Victoria 3010, Australia
⁴ The University of Newcastle, Austraia

^* To whom correspondence should be addressed. E-mail: mohammad.imtiaz{at}newcastle.edu.au.

Submitted on December 27, 2004
Revised on February 14, 2005
Accepted on 5 July 2005

	Abstract

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 the present study a novel mechanism of Ca2+ store entrainment through depolarization-induced IP3 receptor-mediated Ca2+ 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 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.

Key Words: Ca2+ oscillations, coupled oscillators, entrainment, inositol 1,4,5-trisphosphate (IP3), slow waves, synchronization

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