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

2002; American Society for Clinical Investigation; Volume: 110; Issue: 2 Linguagem: Inglês

10.1172/jci0215672

1558-8238

William A. Chutkow, Jielin Pu, Matthew T. Wheeler, Tomoyuki Wada, Jonathan C. Makielski, Charles Burant, Elizabeth M. McNally,

Ion channel regulation and function

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.