Title: Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1.

Authors: Takashi Miki, Masashi Suzuki, Tadao Shibasaki, Hiroko Uemura, Toshiaki Sato, Kaori Yamaguchi, Haruhiko Koseki, Toshihiko Iwanaga, Haruaki Nakaya, Susuma Seino

Journal, date & volume: Nat. Med., 2002 May , 8, 466-72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11984590

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.