G-Protein-gated Inwardly-Rectifying K⁺ Channels and Large-conductance Calcium-Activated K⁺ Channels Are Involved in C-Type Natriuretic Peptide-Mediated Vasodilation in Human Arteries

Abstract

C-type natriuretic peptide (CNP) hyperpolarizes and relaxes the smooth muscle of blood vessels. We investigated whether G-protein-gated inwardly-rectifying K + channels (GIRK) and large-conductance calciumactivated K + channels (BKCa channels) were involved in CNP-evoked vasodilatation in human arteries. Isometric tension in human gastroepiploic arteries was measured using a wire myograph. Ion channel currents were recorded by the whole-cell patch-clamp technique. The concentration-dependent vasodilation induced by CNP was reduced significantly after inhibition of GIRK channels (by tertiapin-Q) or of BKCa channel (by paxilline). Immunochemical experiments showed that GIRK3 and GIRK4 subunits were expressed in human arteries. CNP also strongly increased the current density of GIRK and BKCa channels in human arterial smooth muscles. This suggested that the GIRK channel was functionally expressed in smooth muscle and vasodilation action was produced by CNP partly by opening the GIRK and BKCa channels in the human artery.

Identification of a unique endoplasmic retention motif in the Xenopus GIRK5 channel and its contribution to oocyte maturation

“…GIRK channels also regulate cell development and differentiation in lung [3] and breast cancer [4,5,6] and mediate vasodilation in smooth muscle cells [7]. GIRK channels form homo or heterotetramers and constitute the native muscarinic K + channel (KACh) activated by the dimer Gβγ.…”

“…From a functional point of view, Kir channels can be classified in four groups: (a) constitutively active Kir channels (classical Kir2.X channels), (b) G protein-coupled inwardly rectifying potassium channels (Kir3.X or GIRK channels regulated by G protein-coupled receptors), (c) ATP-sensitive K + channels (Kir6.X channels tightly linked to cellular metabolism), and (d) K + transport channels (Kir1.x, Kir4.x, Kir5.x, and Kir7.x) [1]. GIRK channels also regulate cell development and differentiation in lung [3] and breast cancer [4][5][6] and mediate vasodilation in smooth muscle cells [7].…”