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.
University of Chicago, Department of Medicine, Section of Cardiology, Chicago, Illinois 60637, USA.
William A
WA
Chutkow
Jielin
J
Pu
Matthew T
MT
Wheeler
Tomoyuki
T
Wada
Jonathan C
JC
Makielski
Charles F
CF
Burant
Elizabeth M
EM
McNally
D000255:Adenosine Triphosphate / Q000378:metabolism; D000788:Angina Pectoris, Variant / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003329:Coronary Vasospasm / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D015221:Potassium Channels / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D002121:Calcium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D000255:Adenosine Triphosphate