Regulation of Arterial Tone by Activation of Calcium-Dependent Potassium Channels

TLDR

Blood pressure and tissue perfusion are partly regulated by intrinsic myogenic vascular tone, yet the molecular determinants of this response remain largely unknown. Increases in intravascular pressure raise intracellular calcium and depolarize the membrane, thereby activating calcium‑activated potassium channels. The study shows that large‑conductance calcium‑activated potassium channels in arterial smooth muscle limit myogenic tone, as blockade with TEA⁺ or CTX depolarizes and constricts pressurized cerebral arteries, while the channels act as a negative feedback mechanism to restrain membrane depolarization and vasoconstriction.

Abstract

Blood pressure and tissue perfusion are controlled in part by the level of intrinsic (myogenic) vascular tone. However, many of the molecular determinants of this response are unknown. Evidence is now presented that the degree of myogenic tone is regulated in part by the activation of large-conductance calcium-activated potassium channels in arterial smooth muscle. Tetraethylammonium ion (TEA+) and charybdotoxin (CTX), at concentrations that block calcium-activated potassium channels in smooth muscle cells isolated from cerebral arteries, depolarized and constricted pressurized cerebral arteries with myogenic tone. Both TEA+ and CTX had little effect on arteries when intracellular calcium was reduced by lowering intravascular pressure or by blocking calcium channels. Elevation of intravascular pressure through membrane depolarization and an increase in intracellular calcium may activate calcium-activated potassium channels. Thus, these channels may serve as a negative feedback pathway to control the degree of membrane depolarization and vasoconstriction.