Effect of Gating Charges on Mediating the Dual Activation of BK Channels in Smooth Muscle Cells: A Computational Study.

Abstract

This paper employs a computational model to study the dual gating modalities of BK channels in smooth muscles. These channels are gated by both membrane potential and intracellular calcium concentration. It has been previously reported that the sensors for these two stimuli are located at different regions of the channel. Thus, the two sensing modalities act independent of each other. Yet, they result in a concerted and synergistic opening of the channel pore. In this paper, we investigate the effects of these two gating mechanisms by computing the effective gating charges contributed by the channel's voltage and calcium sensors. Along with their independent contributions, we study and estimate the interplay and effect of these two modalities on the channel's activation. The voltage and calcium sensors appear to share the 'load' of the gating charges required to activate the channel based on the cytosolic calcium concentration and membrane potential. Thus, through our computational model, we demonstrate how the two independent sensors gate and coordinate the activation of the channel.