Membrane potential governs calcium influx into microvascular endothelium: integral role for muscarinic receptor activation

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp6806-list-0001">Endothelial function in resistance vessels entails Ca²⁺ and electrical signalling to promote vasodilatation and increase tissue blood flow. Whether membrane potential (V m) governs intracellular calcium concentration ([Ca²⁺]i) of the endothelium remains controversial.[Ca²⁺]i and V m were evaluated simultaneously during intracellular current injection using intact endothelial tubes freshly isolated from mouse skeletal muscle resistance arteries.[Ca²⁺]i did not change during hyperpolarization or depolarization under resting conditions. However in the presence of 100 nM ACh (∼EC50), [Ca²⁺]i increased during hyperpolarization and decreased during depolarization. These responses required extracellular Ca²⁺ and were attenuated by half with genetic ablation of TRPV4 channels.In native microvascular endothelium, half‐maximal stimulation of muscarinic receptors enables V m to govern [Ca²⁺]i by activating Ca²⁺‐permeable channels in the plasma membrane. This effect of V m is absent at rest and can be masked during maximal receptor stimulation.