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ATP-sensitive potassium channels (KATP) regulate a range of biological activities by coupling membrane excitability to the cellular metabolic state. In particular, it has been proposed that KATP channels and specifically, the channel subunits Kir6.1 and SUR2B, play an important role in the regulation of vascular tone. However, recent experiments have suggested that KATP channels outside the vascular smooth muscle compartment are the key determinant of the observed behavior. Thus, we address the importance of the vascular smooth muscle KATP channel, using a novel murine model in which it is possible to conditionally delete the Kir6.1 subunit. Using a combination of molecular, electrophysiological, in vitro, and in vivo techniques, we confirmed the absence of Kir6.1 and KATP currents and responses specifically in smooth muscle. Mice with conditional deletion of Kir6.1 showed no obvious arrhythmic phenotype even after provocation with ergonovine. However, these mice were hypertensive and vascular smooth muscle cells failed to respond to vasodilators in a normal fashion. Thus, Kir6.1 underlies the vascular smooth muscle KATP channel and has a key role in vascular reactivity and blood pressure control.

Original publication

DOI

10.1161/HYPERTENSIONAHA.114.03116

Type

Journal article

Journal

Hypertension

Publication Date

09/2014

Volume

64

Pages

523 - 529

Keywords

KATP, blood pressure, muscle, smooth, Animals, Blood Pressure, Calcitonin Gene-Related Peptide, Disease Models, Animal, Hypertension, In Vitro Techniques, KATP Channels, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Smooth, Vascular, Patch-Clamp Techniques, Pinacidil, Vasodilator Agents