Effect of progesterone on calcium activated potassium currents and intracellular calcium in guinea pig colon myocytes

Aims: To study the effects of progesterone on contractile activity of smooth muscle strips and on ion currents and intracellular Ca2+([Ca2+])i) intensity in single colonic myocytes in guinea pig proximal colons. Methods: Strips and single cells were dissected from female guinea pig proximal colon. Contraction of strips through an isotonic transducer was assessed and the responsible currents to progesterone were recorded with EPC-9 amplifier in nystatin perforated whole-cell configuration. Detection of [Ca2+]i fluorescence loading fura-2 acetoxymethylester (fura-2/AM) was measured with confocal microscope. Results: Progesterone significantly inhibited contraction of guinea pig colors strips in a dose-dependent pattern. Inhibitory concentration 50(IC50) of progesterone in longitudinal strips and circular strips was, respctively, 9.7 mu M and 1.0 mu M. lberiotoxin (IbTX) partially blocked inhibition of progesterone in both oriented smooth muscle strips. Ca2+ activated K+ (K-Ca) channel currents recorded by depolarizing pulse protocol were enhanced by progesterone to 138% +/- 13%a (n = 9, p < 0.01), and to 143% +/- 12% (n = 8. p < 0.01) when per fused with 10 mu M onapristone. Progesterone reduced L-Ca2+ currents to 67% +/- 6% (n = 7, p < 0.01) and had no effect with 51 mu M nicardipine in bath solution. [Ca2+]i fluorescence was reduced by progesterone to 75% +/- 12% (n = 8, p < 0.01). Conclusions: Progesterone decreases the contraction of colonic smooth muscles by enhancing K-Ca currents and reducing Ca2+ influx. (c) 2005 Pious Science. All rights reserved.