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

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.