Endothelial caveolar modulation of SK3 channel activity

Abstract

Small‐ and intermediate‐conductance Ca2+‐activated K+ channels (SK3/Kcnn3 and IK1/Kcnn4) are expressed in vascular endothelium. Their activities play important roles in regulating vascular tone through their modulation of [Ca2+]i required for the production of endothelium‐derived vasoactive agents. Activation of endothelial IK1 or SK3 channels hyperpolarizes endothelial cell membrane potential, increases Ca2+ influx, and leads to the release of vasoactive factors, thereby impacting blood pressure. To examine the distinct roles of IK1 and SK3 channels, we used electrophysiological recordings to investigate IK1 and SK3 channel trafficking in acutely dissociated endothelial cells from mouse aorta. The results show that SK3 channels undergo Ca2+‐dependent cycling between the plasma membrane and intracellular organelles; disrupting Ca2+‐dependent endothelial caveolae cycling abolishes SK3 channel trafficking. Moreover, transmitter induced changes in SK3 channel activity and surface expression modulate endothelial membrane potential. In contrast, IK1 channels do not undergo rapid trafficking and their activity remains unchanged when either exo‐ or endocytosis is block. Thus, modulation of SK3 surface expression may play an important role in regulating endothelial membrane potential in a Ca2+‐dependent manner.