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 mu rine model of experimental colitis, Colonic myocytes from dextran sulphate sodium (DSS)-treated mice were examined by whole cell patch clamp technique s. Myeloperoxidase activity was enhanced 3.5-fold in DSS-treated mouse colo n. In whole cell voltage clamp, depolarization predominantly evoked net tra nsient outward currents in DSS-treated mice and inward Ca2+ currents in con trol myocytes. Voltage-dependent L-type Ca2+ currents were studied using in tracellular Cs+ in the patch pipette. Inward Ca2+ currents were markedly su ppressed 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 DS S mice. In contrast there was no change in the amplitude, kinetics, or stea dy-state inactivation properties of the transient outward currents in contr ol or DSS-treated colonic myocytes. Inflammation significantly enhanced act ivation 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. T hese 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. (C) 2000 Academic Press.