KIR channels function as electrical amplifiers in rat vascular smooth muscle

• Published in: The Journal of physiology 2008-02, Vol.586 (4), p.1147-1160
• Main Authors: Smith, Pamela D., Brett, Suzanne E., Luykenaar, Kevin D., Sandow, Shaun L., Marrelli, Sean P., Vigmond, Edward J., Welsh, Donald G.
• Format: Article
• Language: English
• Subjects: Animals; Barium - pharmacology; Cardiovascular; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Female; Models, Biological; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - physiology; Patch-Clamp Techniques; Potassium - metabolism; Potassium Channels, Inwardly Rectifying - drug effects; Potassium Channels, Inwardly Rectifying - physiology; Rats; Rats, Sprague-Dawley; Vasodilation - drug effects; Vasodilation - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2007.145474

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.