Episodic coronary artery vasospasm and hypertension develop in the absence of Sur2 KATP channels

Abstract

K ATP channels couple the intracellular energy state to membrane excitability and regulate a wide array of biologic activities. K ATP channels contain a pore-forming inwardly rectifying potassium channel and a sulfonylurea receptor regulatory subunit (SUR1 or SUR2). To clarify the role of K ATP channels in vascular smooth muscle, we studied Sur2 gene-targeted mice (Sur2 -/- ) and found significantly elevated resting blood pressures and sudden death. Using in vivo monitoring, we detected transient, repeated episodes of coronary artery vasospasm in Sur2 -/- mice. Focal narrowings in the coronary arteries were present in Sur2 -/- mice consistent with vascular spasm. We treated Sur2 -/- mice with a calcium channel antagonist and successfully reduced vasospastic episodes. The intermittent coronary artery vasospasm seen in Sur2 -/- mice provides a model for the human disorder Prinzmetal variant angina and demonstrates that the SUR2 K ATP channel is a critical regulator of episodic vasomotor activity.