K IR channels function as electrical amplifiers in rat vascular smooth muscle

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 μ m 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.