Linking Hyperpolarization to Endothelial Cell Calcium Events in Arterioles

Our understanding of the relationship between EC membrane potential and Ca2+ entry has been shaped historically by data from cells in culture. Membrane hyperpolarization was associated with raised cytoplasmic [Ca2+] ascribed to the increase in the inward electrochemical gradient for Ca2+, as ECs are generally thought to lack VGCC. Ca2+ influx was assumed to reflect the presence of an undefined Ca2+ leak channel, although the original research articles with isolated ECs did not elucidate which Ca2+ influx channel was involved or indeed if a transporter might contribute. Overall, these early studies left many unanswered questions, not least whether a similar mechanism operates in native ECs that are coupled to each other and, in many smaller arteries and arterioles, to the adjacent vascular SMCs via gap junctions. This review discusses whether Ca2+ leak through constitutively active EC Ca2+ channels or a more defined, gated pathway might underlie the reported link between enhanced Ca2+ entry and hyperpolarization. Electrophysiological evidence from ECs in isolation is compared with those in intact arteries and arterioles and the possible physiological relevance of EC Ca2+ entry driven by hyperpolarization discussed.