Ion channels and the regulation of myogenic tone in peripheral arterioles

Myogenic tone is a hall-mark feature of arterioles in the microcirculation. This pressure-induced, contractile activation of vascular smooth muscle cells (VSMCs) in the wall of these microvessels importantly contributes to the regulation and maintenance of blood pressure; blood flow to and within organs and tissues; and capillary pressure and fluid balance. Ion channels play a central role in the genesis and maintenance of myogenic tone. Mechanosensitive ion channels such as TRPC6 may serve as one of the sensors of pressure-induced membrane stress/strain, and TRPC6 along with TRPM4 channels are responsible pressure-induced VSMC depolarization that may be bolstered by the activity of Ca²⁺-activated Cl^- channels and inhibition of voltage-gated K⁺ (K_V) channels, inwardly-rectifying K⁺ (K_IR) channels and ATP-sensitive K⁺ (K_ATP) channels. Membrane potential depolarization activates voltage-gated Ca²⁺ channels (VGCCs), with CaV1.2 channels playing a central role. Calcium entry through CaV1.2 channels, which is amplified by Ca²⁺ release through IP₃ receptors in the form of Ca²⁺ waves in some arterioles, provides the major source of activator calcium responsible for arteriolar myogenic tone. Stabilizing negative-feedback comes from depolarization- and Ca²⁺-induced activation of large-conductance Ca²⁺-activated K⁺ channels and depolarization-induced activation of K_V channels. Myogenic tone also is dampened by tonic activity of K_IR and K_ATP channels. While much has been learned about ion channel expression and function in myogenic tone, additional studies are required to fill in our knowledge gaps due to significant regional differences in ion channel expression and function and a lack of data specifically from VSMCs in arterioles.