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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

191 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)203-208
Number of pages6
JournalJournal of Clinical Investigation
Volume110
Issue number2
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Medicine(all)

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