Function and distribution of the SUR isoforms and splice variants.
Alternative splicing allows multiple mRNAs to be generated from a single gene, which in turn can be translated into a group of diverse proteins with different roles and structures. The outcome of alternative splicing leads to the co-existence of multiple splice variants of a gene at different concentrations in different tissues. The pore-forming subunit of the K(ATP) channel (K(IR)6.x) and the regulatory sulfonylurea receptor (SUR(x)) subunits exist in a 4:4 stoichiometry to form hetero-octameric ATP-sensitive potassium channel (K(ATP)) channels, which are widely distributed in various types of tissues at either the plasma membrane (cellK(ATP)) or mitochondrial inner membrane (the mitochondrial form of K(ATP) channel, mitoK(ATP)). They perform important physiological functions in regulating insulin secretion in pancreatic beta-cells, providing ischemic protection in heart and brain, and regulating vascular tone in smooth muscles. Two separate genes, the regulatory subunit protein I (SUR1) and the regulatory subunit protein II (SUR2) encode the high- and low-affinity SUR, respectively. This review summarizes the current studies on the function and distribution of the SUR isoforms and alternative splice variants, and to a lesser extent the K(IR)6.x subunits. The different isoforms and splice variants allow for many K(ATP) channel combinations, and therefore, increases the channel diversity and the possibility of complexity in function.
Department of Medicine, Cardiovascular Medicine Section, University of Wisconsin, Madison, WI 53705, USA.
Nian-Qing
NQ
Shi
Bin
B
Ye
Jonathan C
JC
Makielski
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D017398:Alternative Splicing; D000818:Animals; D006801:Humans; D019194:Ischemic Preconditioning; D056892:Mediator Complex; D051379:Mice; D018345:Mice, Knockout; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D021122:Protein Subunits; D021381:Protein Transport; D011955:Receptors, Drug / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D064233:Sulfonylurea Receptors; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*
C577507:ABCC8 protein, human; C577510:ABCC9 protein, human; D018528:ATP-Binding Cassette Transporters; C577508:Abcc8 protein, mouse; C492159:MED23 protein, human; D056892:Mediator Complex; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D015534:Trans-Activators; C117780:mitochondrial K(ATP) channel