KATP channels couple the intracellular energy state to membrane excitability and regulate a wide array of biologic activities. KATP channels contain a pore-forming inwardly rectifying potassium channel and a sulfonylurea receptor regulatory subunit (SUR1 or SUR2). To clarify the role of KATP 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 KATP channel is a critical regulator of episodic vasomotor activity.
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