Altered Ion Channel Activity in Murine Colonic Smooth Muscle Myocytes in an Experimental Colitis Model

Abstract

We have investigated the activity of calcium and potassium channels in a murine model of experimental colitis. Colonic myocytes from dextran sulphate sodium (DSS)-treated mice were examined by whole cell patch clamp techniques. Myeloperoxidase activity was enhanced 3.5-fold in DSS-treated mouse colon. In whole cell voltage clamp, depolarization predominantly evoked net transient outward currents in DSS-treated mice and inward Ca2+ currents in control myocytes. Voltage-dependent L-type Ca2+ currents were studied using intracellular Cs+ in the patch pipette. Inward Ca2+ currents were markedly suppressed in inflamed colon. The peak currents at +10 mV depolarization were −3.93 ± 0.88 pA/pF in control (n = 12) and −1.14 ± 0.19 (n = 10) in DSS mice. In contrast there was no change in the amplitude, kinetics, or steady-state inactivation properties of the transient outward currents in control or DSS-treated colonic myocytes. Inflammation significantly enhanced activation of the ATP-sensitive K+ channel. At a holding potential of −50 mV, the KATP channel opener lemakalim induced an inward current of 2.02 ± 0.5 pA/pF in control (n = 20) and 4.19 ± 1.17 pA/pF in DSS-treated colon. These currents were abolished by glibenclamide. The present results suggest that inflammation of the colon results in selective changes in ion channel activity of smooth muscle cells.