ATP-sensitive K+ (K-ATP) channels couple metabolic changes to membrane excitability in vascular smooth muscle cells (SMCs). While the electrophysiological properties of K-ATP channels have been examined, little is known about the molecular basis of K-ATP complex in vascular SMCs. We identified and cloned four K-ATP subunit genes from rat mesenteric artery, namely rvKir6.1, rvKir6.2, rvKirSUR1, and rvSUR2B. These clones showed over 99.6% amino acid sequence identity with other previously reported isoforms. The mRNA expression patterns of the K-ATP subunits varied among rat aorta, mesenteric artery, pulmonary artery, tail artery, hepatic artery, and portal vein. Heterologous co-expression of rvKir6.1 and rvSUR2B yielded functional K-ATP channels that were inhibited by glibenclamide, and opened by pinacidil. Our results for the first time reported the expression of four K-ATP subunits in same vascular tissues, unmasking the diversity of native K-ATP channels in vascular SMCs. (C) 2002 Elsevier Science (USA). All rights reserved.