Channelpedia

PubMed 16186562


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ1 , Kv7.1 , SK3 , Slo1



Title: Pharmacological properties and functional role of Kslow current in mouse pancreatic beta-cells: SK channels contribute to Kslow tail current and modulate insulin secretion.

Authors: Min Zhang, Khaled Houamed, Sabina Kupershmidt, Dan Roden, Leslie S Satin

Journal, date & volume: J. Gen. Physiol., 2005 Oct , 126, 353-63

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16186562


Abstract
The pharmacological properties of slow Ca(2+)-activated K(+) current (K(slow)) were investigated in mouse pancreatic beta-cells and islets to understand how K(slow) contributes to the control of islet bursting, [Ca(2+)](i) oscillations, and insulin secretion. K(slow) was insensitive to apamin or the K(ATP) channel inhibitor tolbutamide, but UCL 1684, a potent and selective nonpeptide SK channel blocker reduced the amplitude of K(slow) tail current in voltage-clamped mouse beta-cells. K(slow) was also selectively and reversibly inhibited by the class III antiarrythmic agent azimilide (AZ). In isolated beta-cells or islets, pharmacologic inhibition of K(slow) by UCL 1684 or AZ depolarized beta-cell silent phase potential, increased action potential firing, raised [Ca(2+)](i), and enhanced glucose-dependent insulin secretion. AZ inhibition of K(slow) also supported mediation by SK, rather than cardiac-like slow delayed rectifier channels since bath application of AZ to HEK 293 cells expressing SK3 cDNA reduced SK current. Further, AZ-sensitive K(slow) current was extant in beta-cells from KCNQ1 or KCNE1 null mice lacking cardiac slow delayed rectifier currents. These results strongly support a functional role for SK channel-mediated K(slow) current in beta-cells, and suggest that drugs that target SK channels may represent a new approach for increasing glucose-dependent insulin secretion. The apamin insensitivity of beta-cell SK current suggests that beta-cells express a unique SK splice variant or a novel heteromultimer consisting of different SK subunits.