ATP‐Sensitive K⁺ Channels of Vascular Smooth Muscle Cells

Abstract

ATP-sensitive potassium channels (K(ATP)) of vascular smooth muscle cells represent potential therapeutic targets for control of abnormal vascular contractility. The biophysical properties, regulation and pharmacology of these channels have received intense scrutiny during the past twenty years, however, the molecular basis of vascular K(ATP) channels remains ill-defined. This review summarizes the recent advancements made in our understanding of the molecular composition of vascular K(ATP) channels with a focus on the evidence that hetero-octameric complexes of Kir6.1 and SUR2B subunits constitute the vascular K(ATP) subtype responsible for control of arterial diameter by vasoactive agonists.

Forkhead Transcription Factors Coordinate Expression of Myocardial KATP Channel Subunits and Energy Metabolism

“…The potassium channel pore consists of 4 KIR6.2 subunits in left ventricle, 11 pancreatic ␤-cells, 12 and vascular endothelium 13 and mainly of 4 KIR6.1 subunits in vascular smooth muscle. 14 The brain 2 and skeletal muscle 15 express both KIR6.1 and KIR6.2. The same cardiac tissue may change its subunit composition: subunit Kir6.1 is increasingly expressed in left ventricle following ischemia, 16 exercise, 17 or treatment with K ATP channel agonist.…”

Ion channels of the mammalian urethra

“…38,46 Important physiological implications result from the particular heterotetrameric arrangement of the channel complex identified in the urethra that distinguish it from other smooth muscle types such as those found in vascular tissues. 52,53 The gating properties (i.e., activation) of the heterotetrameric K ATP channel complex found in the urethra can be dynamically modulated by protein kinase C (PKC), 38 which is distinct from the mechanism observed in vascular smooth muscle for K ATP channels. 53 Voltage and Ca 2C -activated K C channels Following elucidation of the role of K ATP channels in urethral smooth muscle cells, the next series of breakthroughs in characterizing urethral smooth muscle cell ion channel properties originated from a collaboration among the Hollywood, McHale and Thornbury laboratories investigating K C channels and voltage-gated Ca 2C channels (VGCCs, Fig.…”

Proteomic analysis of the effect of iptakalim on human pulmonary arterial smooth muscle cell proliferation

“…Furthermore, activation of K + channels can induce apoptosis in vascular SMCs [8] . Recently, K ATP channels have received intense scrutiny because of their biophysical properties, regulation and pharmacology [9] . Vasoactive agonists such as ET-1 can alter the activity of K ATP channels in vascular SMCs, which contributes to the regulation of arterial diameter [10] .…”

“…Vasoactive agonists such as ET-1 can alter the activity of K ATP channels in vascular SMCs, which contributes to the regulation of arterial diameter [10] . This observation has prompted a widespread interest in K ATP channels as potential targets to regulate proliferative vascular disorders in disease conditions such as PH [9] . Iptakalim (Ipt), a lipophilic para-amino compound with a low molecular weight, has been demonstrated via pharmacological, electrophysiological, and biochemical studies and a receptor binding test to be a new selective K ATP channel opener [11,12] .…”