Abstract：
:The inwardly rectifying K(+) channel Kir6.1 forms K(+) channels by coupling with a sulfonylurea receptor in reconstituted systems, but the physiological roles of Kir6.1-containing K(+) channels have not been determined. We report here that mice lacking the gene encoding Kir6.1 (known as Kcnj8) have a high rate of sudden death associated with spontaneous ST elevation followed by atrioventricular block as seen on an electrocardiogram. The K(+) channel opener pinacidil did not induce K(+) currents in vascular smooth-muscle cells of Kir6.1-null mice, and there was no vasodilation response to pinacidil. The administration of methylergometrine, a vasoconstrictive agent, elicited ST elevation followed by cardiac death in Kir6.1-null mice but not in wild-type mice, indicating a phenotype characterized by hypercontractility of coronary arteries and resembling Prinzmetal (or variant) angina in humans. The Kir6.1-containing K(+) channel is critical in the regulation of vascular tonus, especially in the coronary arteries, and its disruption may cause Prinzmetal angina.
journal_name
Nat Medjournal_title
Nature medicineauthors
Miki T,Suzuki M,Shibasaki T,Uemura H,Sato T,Yamaguchi K,Koseki H,Iwanaga T,Nakaya H,Seino Sdoi
10.1038/nm0502-466keywords:
subject
Has Abstractpub_date
2002-05-01 00:00:00pages
466-72issue
5eissn
1078-8956issn
1546-170Xpii
nm0502-466journal_volume
8pub_type
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