K_IR channels function as electrical amplifiers in rat vascular smooth muscle

Abstract

Strong inward rectifying K(+) (K(IR)) channels have been observed in vascular smooth muscle and can display negative slope conductance. In principle, this biophysical characteristic could enable K(IR) channels to 'amplify' responses initiated by other K(+) conductances. To test this, we have characterized the diversity of smooth muscle K(IR) properties in resistance arteries, confirmed the presence of negative slope conductance and then determined whether K(IR) 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 K(IR) channels were highly expressed in cerebral and coronary, but not mesenteric arteries. These channels comprised K(IR)2.1 and 2.2 subunits and electrophysiological recordings demonstrated that they display negative slope conductance. Computational modelling predicted that a K(IR)-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 mum Ba(2+) attenuated the ability of K(+) channel activators to dilate cerebral and coronary arteries. This attenuation was absent in mesenteric arteries where smooth muscle K(IR) channels were poorly expressed. In summary, smooth muscle K(IR) 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 K(IR) have a substantive, albeit indirect, role in enabling agonists to alter the electrical state of a multilayered artery.