Synchronization of Ca2+ oscillations through voltage-dependent modulation of store Ca2+ release

University of Bristol (2005) J Physiol 567P, C95

Oral Communications: Synchronization of Ca2+ oscillations through voltage-dependent modulation of store Ca2+ release

Imtiaz, Mohammad Shariq; Katnik, Christopher; Smith, David W; van Helden, Dirk F;

1. The Neuroscience Group, The School of Biomedical Sciences, The University of Newcastle, Callaghan, NSW, Australia. 2. Pharmacology and Therapeutics, University of Southern Florida, Tampa, FL, USA. 3. Department of Civil and Environmental Engineering, The University of Melbourne, Melbourne, VIC, Australia.

View other abstracts by:


The mechanical activity of many smooth muscles is controlled by a cyclical depolarization known as slow waves (Bolton, 1971). 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 (van Helden & Imtiaz, 2003). It has been shown that IP3 receptor-mediated Ca2+ release is enhanced by membrane depolarization (Suzuki & Hirst, 1999; van Helden et al. 2000), and it is this positive feedback that underlies the long-range entrainment of Ca2+ stores. The present study examines the mechanisms underlying such store entrainment. In gap junction connected cells diffusion of Ca2+ or IP3 across gap junctions have been implicated in synchronization of Ca2+ oscillations. In the present study we investigate Ca2+ store entrainment through depolarization-induced IP3 receptor-mediated Ca2+ release. This mechanism is significantly different from the chemical coupling-based class of models as membrane potential has a coupling effect over distances several orders of magnitude greater than either diffusion of Ca2+ or IP3 through gap junctions. Experimental observations predicate that electrically coupled cells can interact and modulate Ca2+ excitability and oscillations of other cells through voltage dependent enhancement of store Ca2+ release. We encapsulate this in a model where; 1) each local oscillator is composed of a cytosolic-store Ca2+ excitable system, 2) local Ca2+ oscillations are coupled to membrane potential, and, 3) membrane potential influences the local Ca2+ oscillator through a positive feedback loop. We construct a coupled cell pair according to the schema outlined above using our previously presented single cell model (Imtiaz et al. 2002). Here we use voltage-dependent IP3 synthesis to model the positive feedback of membrane potential on cytosolic-store excitability. The effect of electrical coupling strength on synchronization of a cell pair is studied. It is shown that weak electrical coupling is sufficient to synchronize even heterogeneous cell pairs. A comparison is made between electrical and chemical coupling (through diffusion of Ca2+ or IP3). It is shown that chemical coupling is not effective when cells are weakly coupled and have different intrinsic frequencies. The result of this study show that electrical coupling acting through voltage-dependent modulation of store Ca2+ release is able to synchronize oscillations of cells even when cells are weakly coupled (or widely separated) and/or have different intrinsic frequencies of oscillation.



Where applicable, experiments conform with Society ethical requirements.

Site search

Filter

Content Type