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.
Akbarali
H I
HI
Center for Swallowing and Motility Disorders, West Roxbury, Massachusetts 02132, USA. hakbarali@hms.harvard.edu
Pothoulakis
C
C
Castagliuolo
I
I
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology*; D003106:Colon / Q000166:cytology / Q000502:physiology*; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*
D015220:Calcium Channels; D015221:Potassium Channels; D016264:Dextran Sulfate