Optical Recordings of Ca2+ Influx via TRPV4 and Voltage-Gated L-type Ca2+ Channels in Arterial Smooth Muscle

Abstract

In arterial smooth muscle, L-type Ca2+ channels play a critical role in multiple physiological processes including excitability, contraction, and gene expression. Recent work suggests that TRPV4 channels are also important contributors to Ca2+ influx in these cells. We used optical approaches to record Ca2+ sparklets produced by Ca2+ influx via TRPV4 and L-type Ca2+ channels in arterial myocytes under physiological conditions. We found that TRPV4 and L-type Ca2+ sparklet activity varies throughout the sarcolemmal of arterial myocytes. Our data suggest that these regional variations in sparklet activity arise from interactions between channels, the scaffolding protein AKAP150, and associated proteins at only a few sub-sarcolemmal regions in arterial smooth muscle cells. We will present data obtained using biochemical and optogenetic approaches to investigate the mechanisms leading to subcellular variations in TRPV4 and L-type Ca2+ sparklet activity as well as the functional consequences of these local Ca2+ signals in arterial smooth muscle. These findings will form the basis for a new model for the local control and amplification Ca2+ influx via TRPV4 and voltage-gated L-type Ca2+ channels in resistance artery smooth muscle.