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 (SURx) 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 KIR6.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. (c) 2005 Elsevier Ltd. All rights reserved.