The Effects Of Progesterone And 5-HT On Ion Currents And Membrane Potentials Of Guinea Pig Colon Myocytes

Objective: To investigate the effects of progesterone and 5-HT on spontaneous contraction of muscle strips and the ionic channels currents of single guinea pig proximate colon.Methods: Strips and single cells were separated acutely from female guinea pig proximal colon. Contractions of strips were measured by TD-112S isotonic transducer, Ionic Channels' currents were recorded with an EPC-9 or Axopatch I-D amplifier under conventional whole cell patterns.Result: 1. 64.8 u mol L-1 progesterone produced longitudinal strips significantly relaxation (0.1792g±0.0873g, n=6, P<0.05). Progesterone resulted in concentration dependent relaxation of circular colonic smooth muscle strips (162pmol L-1, 0.2360g±0.01578g, n=6, P<0.05; 1.62nmol L-1, 0.4332g±0.2111g, n=6, P<0.01; 3.24nmol L-1, inhibited completely intestine several strips, P<0.01) 12.96 u mol L-1 progesterone suppressed BKca by 60% compared with control (P<0.01), but failed to inhibit BKcain the presence of 5 u mol L-1 nicardipine. 2. Length of cell shortened 21%±1.5% (n=6, P<0.01). Under current clamp peak values of AP in 5-HT reduced to 60%±7.3% (n=7, P<0.001) and fast repolarization time of AP also decreased from 47.53ms ± 4.88ms to 22.96 ms±4.65ms(n=7, P<0.001), while in the parallel tests RP depolarized from -68.4±-3.6mV (n=11) to -18.2 mV±-2.5mV(n=7, P<0.001). BKca Currents depolarized from -60mV to 60m mV enhanced 27% ± 12% (n=8, P<0.01), but had no potency with heparin in pipettes. Ca2± currents depolarized from -60mV to 0mV enhanced 23%±7% (n=7, P<0.01) and had no potency with heparin in pipettes. But nicardipine inhibited currents of Ca2± 9.3%±5.1% (n=3, P<0.01 ) in the parallel tests.Conclusion: 1. Progesterone at low concentration inhibits contraction of circular muscles and BKca of single circular colonic myocytes by reducing influx of extracellular Ca2±. 2. 5-HT directly induced contraction of single colonic myocytes in guinea pig mostly owing to enhancing currents of Ca2+, and reduced fast repolarization time of AP by increasing BKca Currents.