KIR channels function as electrical amplifiers in rat vascular smooth muscle

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Abstract
Strong inward rectifying K+ (KIR) channels have been observed in vascular smooth muscle and can display negative slope conductance. In principle, this biophysical characteristic could enable KIR channels to ‘amplify’ responses initiated by other K+ conductances. To test this, we have characterized the diversity of smooth muscle KIR properties in resistance arteries, confirmed the presence of negative slope conductance and then determined whether KIR inhibition alters the responsiveness of middle cerebral, coronary septal and third-order mesenteric arteries to K+ channel activators. Our initial characterization revealed that smooth muscle KIR channels were highly expressed in cerebral and coronary, but not mesenteric arteries. These channels comprised KIR2.1 and 2.2 subunits and electrophysiological recordings demonstrated that they display negative slope conductance. Computational modelling predicted that a KIR-like current could amplify the hyperpolarization and dilatation initiated by a vascular K+ conductance. This prediction was consistent with experimental observations which showed that 30 μm Ba2+ attenuated the ability of K+ channel activators to dilate cerebral and coronary arteries. This attenuation was absent in mesenteric arteries where smooth muscle KIR channels were poorly expressed. In summary, smooth muscle KIR expression varies among resistance arteries and when channel are expressed, their negative slope conductance amplifies responses initiated by smooth muscle and endothelial K+ conductances. These findings highlight the fact that the subtle biophysical properties of KIR have a substantive, albeit indirect, role in enabling agonists to alter the electrical state of a multilayered artery.