How Spatiotemporal Clustering of L-Type Ca2+ Channels Regulates Ca2+ Signals in Rat Ventricular Myocytes?

Abstract

Calcium flux thought L-type Ca2+ channels (LTCCs) influences numerous physiological processes ranging from contraction of muscle and memory in neurons to gene expression in many type cell types [1,2,3]. The spatiotempotal organization of functional LTCCs, however, is difficult to investigate experimentally because of methodological limitations [2]. In this study, we used our 3-D continuum model of Ca2+ signaling, buffering and diffusion in rat ventricular myocytes to examine the effects of LTCCs ganging up in the sarcolemma during the cell excitation [4]. Model predicts that local and global Ca2+ signals critically depend on the spatiotemporal location of Ca2+ influx via persistent LTCCs, on the branched t-tubule topology and on the local diffusion properties. We tested also the hypothesis that under physiological conditions, the coupled gating of LTCCs may increase the activation probability of Ca2+-dependent proteins involved in contraction and cell excitability [2].[1] Bers, Circ Res 106(4):625-626, 2010[2] Navedo et al, Circ Res 106:784-756, 2010[3] Inoue and Bridge, Circ Res 92:532-538, 2003[4] Cheng et al., PLoS Comp Biol 6(10): article e1000972, 2010Supported by NBCR (NIH grant 5P41 RR08605-17)