We have isolated a cDNA encoding a novel isoform of the sulfonylurea receptor 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 channels. Sequence analysis indicated that this clone is a variant of cardiac type sulfonylurea receptor (SUR2). The 42 amino acid residues located in the carboxyl-terminal end of this novel sulfonylurea receptor is, however, divergent from that of SUR2 but highly homologous to that of the pancreatic one (SUR1). Therefore, this short part of the carboxyl terminus may be important for diazoxide activation of K ATP channels. The reverse transcription-polymerase chain reaction analysis showed that mRNA of this clone was ubiquitously expressed in diverse tissues, including brain, heart, liver, urinary bladder, and skeletal muscle. These results suggest that this novel isoform of sulfonylurea receptor is a subunit reconstituting the smooth muscle K ATP channel.

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A variety of cells including cardiac myocytes and neuronal cells possess inwardly rectifying K+ (Kir) channels through which currents flow more readily in the inward direction than outward. These K+ channels play pivotal roles in maintenance of the resting membrane potential, in regulation of the action potential duration, in receptor-dependent inhibition of cellular excitability, and in the secretion and absorption of K+ ions across cell membrane. Recent molecular biological dissection has shown that the DNAs encoding Kir channels constitute a new family of K+ channels whose subunits contain two putative transmembrane domains and a pore-forming region. So far, more than ten cDNAs of Kir channel subunits have been isolated and classified into four subfamilies: 1) IRK subfamily (IRK1-3/Kir1.1-1.3), 2) GIRK subfamily (GIRK1-4/Kir3.1-3.4), 3) ATP-dependent Kir subfamily (ROMK1/Kir1.1, K(AB)-2/Kir4.1), and 4) ATP-sensitive Kir subfamily (uKATP-1/Kir6.1, BIR/Kir6.2). Xenopus oocytes injected with the cRNAs of IRKs elicit classical Kir channel currents. GIRKs, as heteromultimers, compose the G protein-gated Kir (KG) channels, which are regulated by a variety of Gi/Go-coupled inhibitory neurotransmitter receptors such as m2-mus-carinic, serotonergic (5HT1A), GABAB, somatostatin and opioid (mu, delta, kappa) receptors. ROMK1 and KAB-2 are characterized with a Walker type-A ATP-binding motif in their carboxyl termini, and may be involved in K+ transport in renal epithelial and brain glial cells. uKATP-1 and BIR form with sulfonylurea receptors, the so-called ATP-sensitive K+ channels. Thus, it is a feature of the Kir channel family that each subfamily plays a specific physiological functional role. The (Na+)-activated Kir channels identified electrophysiologically in neurons and cardiac myocytes have not yet been cloned. In this review, we overviewed the current understandings of the features of the molecular structures and functions of the four main subfamilies of Kir channels.

Intraatrial catheter mapping of the right atrium was performed during sinus rhythm in 92 patients: Group I = 43 control patients without paroxysmal atrial fibrillation or sick sinus node syndrome; Group II = 31 patients with paroxysmal atrial fibrillation but without sick sinus node syndrome; and Group III = 18 patients with both paroxysmal atrial fibrillation and sick sinus node syndrome. Atrial electrograms were recorded at 12 sites in the right atrium. The duration and number of fragmented deflections of the atrial electrograms were quantitatively measured. The mean duration and number of fragmented deflections of the 516 atrial electrograms in Group I were 74 +/- 11 ms and 3.9 +/- 1.3, respectively. The criteria for an abnormal atrial electrogram were defined as a duration of greater than or equal to 100 ms or eight or more fragmented deflections, or both. Abnormal atrial electrograms were observed in 10 patients (23.3%) in Group I, 21 patients (67.7%) in Group II and 15 patients (83.3%) in Group III (Group II versus Group I, p less than 0.001; Group III versus Group I, p less than 0.001). The mean number of abnormal electrograms per patient with an abnormal electrogram was 1.3 +/- 0.7 in Group I, 2.5 +/- 1.9 in Group II and 3.5 +/- 2.5 in Group III (Group I versus Group II, p less than 0.01; Group II versus Group III, p less than 0.05). A prolonged and fractionated atrial electrogram characteristic of paroxysmal atrial fibrillation can be closely related to the vulnerability of the atrial muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunolocalization of KAU-2 (Kir4