Altered ion channel activity in murine colonic smooth muscle myocytes in an experimental colitis model.

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 Ca(2+) currents in control myocytes. Voltage-dependent L-type Ca(2+) currents were studied using intracellular Cs(+) in the patch pipette. Inward Ca(2+) 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 K(ATP) 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. Copyright 2000 Academic Press.