Referenced in: none

Automatically associated channels: Kir6.2

Title: Identification and pharmacological characterization of sarcolemmal ATP-sensitive potassium channels in the murine atrial HL-1 cell line.

Authors: Jocelyn E Manning Fox, Lynn Jones, Peter E Light

Journal, date & volume: J. Cardiovasc. Pharmacol., 2005 Jan , 45, 30-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15613976

Abstract
Activation of ATP-sensitive potassium (KATP) channels is known to have cardioprotective effects during periods of ischemia and reperfusion, making these channels important targets for clinical drug discovery. Using electrophysiological techniques we identify KATP channels in a mouse atrial cell line (HL-1). HL-1 KATP channels exhibited a concentration-dependent inhibition by ATP (IC50 = 23.3 +/- 3.2 microM), a unitary single-channel conductance of 55 pS, and sensitivity to the isoform-specific KATP channel opener P1075 and inhibitor HMR1098. Adenoviral infection of a dominant-negative Kir6.2 subunit significantly reduced the P1075-sensitive sarcKATP current. Taken together, the data indicate that HL-1 KATP channels are composed of sulfonylurea receptor isoform SUR2A coupled to the pore-forming Kir6.2 subunit--the molecular makeup of sarcKATP channels found in native cardiac myocytes. Pharmacological activation of HL-1 cell KATP channels also resulted in action potential shortening. Using the membrane potential-sensitive dye DiBac4(3), we demonstrated that the sarcKATP channel opener P1075 (20 microM) produced a concentration-dependent hyperpolarization of a monolayer of HL-1 cells that could be reversed by channel inhibition with HMR1098 (20 microM). We conclude that the HL-1 cells are an excellent cell line for studying cardiac sarcKATP channels, and these cells may also provide an important tool for the testing of novel pharmacological modulators of KATP channels in fluorescence-based assays.