Vanishing Act

Abstract

Potassium channels play an important role in the regulation of vascular smooth muscle tone and, thus, contribute to the regulation of blood pressure, blood flow, and microvascular exchange.1 These channels importantly participate in the determination of vascular smooth muscle cell (VSMC) membrane potential,1,2 which, in turn, controls Ca2+ influx through voltage-gated Ca2+ channels1,2 and has been implicated in the control of Ca2+ release and Ca2+ sensitivity of VSMCs.1 VSMCs express a diverse array of K+ channels that contribute to the regulation of VSMC function,1 including ≥1 type of vascular ATP-sensitive K+ (KATP) channels.2,3 KATP channels consist of a tetramer of α-pore–forming subunits from the KIR6.X family of inwardly rectifying K+ channels, along with complimentary sulfonylurea receptor (SUR) subunits that are members of the ATP-binding cassette family of proteins.2 The SUR subunits are essential for normal trafficking of KATP channels, modulate channel function, and are the binding sites for sulfonylurea antagonists of these channels, such as glibenclamide.2 Vascular smooth muscle KATP channels appear to be composed of KIR6.1 and SUR2B subunits,2 although some VSMCs may also express KATP channels composed of KIR6.2/SUR2B.3 As originally described, KATP channels open during hypoxia or ischemic conditions when cellular ATP levels fall, decreasing cell excitability and protecting energy-limited cells.2 However, both in vitro and in vivo studies suggest that VSMC KATP channels may be open under resting conditions and contribute to the regulation of VSMC membrane potential and vascular tone.1,2 Importantly, the activity of KATP channels can be modulated by a number of physiologically relevant vasoactive substances and conditions. As their name implies, KATP channels may be activated by decreases in intracellular …