A NOVEL SULFONYLUREA RECEPTOR FORMS WITH BIR (KIR6.2) A SMOOTH-MUSCLETYPE ATP-SENSITIVE K+ CHANNEL

We have isolated a cDNA encoding a novel isoform of the sulfonylurea r eceptor from a mouse heart cDNA library. Coexpression of this isoform and BIR (Kir6.2) in a mammalian cell line elicited ATP-sensitive K+ (K -ATP) channel currents. The channel was effectively activated by both diazoxide and pinacidil, which is the feature of smooth muscle K-ATP c hannels. Sequence analysis indicated that this clone is a variant of c ardiac type sulfonylurea receptor (SUR2), The 42 amino acid residues l ocated in the carboxyl-terminal end of this novel sulfonylurea recepto r is, however, divergent from that of SURE but highly homologous to th at of the pancreatic one (SUR1). Therefore, this short part of the car boxyl terminus may be important for diazoxide activation of K-ATP chan nels, The reverse transcription-polymerase chain reaction analysis sho wed that mRNA of this clone was ubiquitously expressed in diverse tiss ues, including brain, heart, liver, urinary bladder, and skeletal musc le. These results suggest that this novel isoform of sulfonylurea rece ptor is a subunit reconstituting the smooth muscle K-ATP channel.