Programme Contents

Synchronization of Ca²⁺ oscillations through interaction of intracellular Ca²⁺ stores and L-type Ca²⁺ channels

Many lymphatic and blood vessels undergo spontaneous constriction-dilation cycle known as vasomotion. It has been shown that cyclical Ca²⁺ release from inositol 1,4,5-trisphosphate (IP₃) operated intracellular Ca²⁺ stores and influx of Ca²⁺ through L-Ca²⁺ channels underlie lymphatic vasomotion (Zhao & van Helden, 2003). Experimental observations show that blocking L-Ca²⁺ channels abolishes synchronous Ca²⁺ oscillations, leaving only asynchronous oscillations. Based on such experimental observations and theoretical studies, we have previously shown that L-Ca²⁺ channels form a long-range coupling link between oscillatory Ca²⁺ stores, and are essential for synchronization of store Ca²⁺ release (Imtiaz et al., 2002; Zhao et al., 2002). The present study examines this L-Ca²⁺ channel-mediated long-range coupling mechanism.

Synchronization of Ca²⁺ oscillations can occur through diffusion of Ca²⁺ or IP₃ through gap junctions. In the present study we investigate Ca²⁺ store entrainment through voltage dependent L-Ca²⁺ channel-mediated store Ca²⁺ release for a cell pair. Such a coupling mechanism is significantly more effective than 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 (Imtiaz et al., 2002).

We encapsulate experimental observations 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 exerts a positive feedback on the local Ca²⁺ oscillator through Ca²⁺ influx through L-Ca²⁺ channels. We construct a coupled cell pair according to the schema outlined above.

We study the synchronization properties of the above cell pair system. It is shown that even weak electrical coupling is sufficient to synchronize 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. This is consistent with experimental observations where only asynchronous oscillations are observed during blockade of L-Ca²⁺ channels. The result of this study show that electrical coupling acting through L-Ca²⁺-mediated 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.

Imtiaz, M., Zhao, J., & van-Helden, D.F. (2002) Proceedings of the Australian Physiological and Pharmacological Society http://www.aups.org.au/Meetings/200211/abstracts/1148.html

Zhao, J., Imtiaz, M., and van Helden, D. (2002) Proceedings of the Australian Physiological and Pharmacological Society http://www.aups.org.au/Meetings/200211/abstracts/1149.html

Zhao, J. & van Helden, D.F. (2003) British Journal of Pharmacology 140, 1399-1413.