| First Author | Miki T | Year | 2002 |
| Journal | Nat Med | Volume | 8 |
| Issue | 5 | Pages | 466-72 |
| PubMed ID | 11984590 | Mgi Jnum | J:76195 |
| Mgi Id | MGI:2178850 | Doi | 10.1038/nm0502-466 |
| Citation | Miki T, et al. (2002) Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1. Nat Med 8(5):466-72 |
| abstractText | 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. |
