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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphate / metabolism
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Angina Pectoris, Variant / etiology
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Angina Pectoris, Variant / genetics
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Angina Pectoris, Variant / metabolism
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Animals
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Calcium Channel Blockers / therapeutic use
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Coronary Vasospasm / drug therapy
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Coronary Vasospasm / etiology*
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Coronary Vasospasm / genetics
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Coronary Vasospasm / metabolism
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Death, Sudden, Cardiac / etiology
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Disease Models, Animal
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Female
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Humans
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Hypertension / etiology*
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Hypertension / genetics
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Hypertension / metabolism
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In Vitro Techniques
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Male
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Mice
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Mice, Knockout
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Muscle, Smooth, Vascular / metabolism
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Potassium Channels / deficiency*
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Potassium Channels / genetics
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Potassium Channels / metabolism
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Potassium Channels, Inwardly Rectifying / deficiency*
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Potassium Channels, Inwardly Rectifying / genetics
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Potassium Channels, Inwardly Rectifying / metabolism
Substances
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Calcium Channel Blockers
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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Adenosine Triphosphate