TY - JOUR
T1 - Effect of progesterone on calcium activated potassium currents and intracellular calcium in guinea pig colon myocytes
AU - Xu, L.
AU - Chen, J.
AU - Yu, Baoping
AU - Dong, W.
AU - Chen, K.
AU - Luo, H.
AU - Zhu, Y.
PY - 2005/9
Y1 - 2005/9
N2 - 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 colonie 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 [Ca 2+]i fluorescence loading fura-2 acetoxymethylester (fura-2/AM) was measured with confocal microscope. Results: Progesterone significantly inhibited contraction of guinea pig colon strips in a dose-dependent pattern. Inhibitory concentration 50 (IC50) of progesterone in longitudinal strips and circular strips was, respectively, 9.7 μM and 1.0 nM. Iberiotoxin (IbTX) partially blocked inhibition of progesterone in both oriented smooth muscle strips. Ca2+ activated K+ (Kca) channel currents recorded by depolarizing pulse protocol were enhanced by progesterone to 138% ± 13% (n = 9, p < 0.01), and to 143% ± 72% (n = 8, p < 0.01) when perfused with 10 μM onapristone. Progesterone reduced L-Ca2+ currents to 67% ± 6% (n = 7, p < 0.01) and had no effect with 5 μM nicardipine in bath solution. [Ca2+]i fluorescence was reduced by progesterone to 75% ± 72% (n = 8, p < 0.01). Conclusions: Progesterone decreases the contraction of colonic smooth muscles by enhancing KCa currents and reducing Ca + influx.
AB - 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 colonie 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 [Ca 2+]i fluorescence loading fura-2 acetoxymethylester (fura-2/AM) was measured with confocal microscope. Results: Progesterone significantly inhibited contraction of guinea pig colon strips in a dose-dependent pattern. Inhibitory concentration 50 (IC50) of progesterone in longitudinal strips and circular strips was, respectively, 9.7 μM and 1.0 nM. Iberiotoxin (IbTX) partially blocked inhibition of progesterone in both oriented smooth muscle strips. Ca2+ activated K+ (Kca) channel currents recorded by depolarizing pulse protocol were enhanced by progesterone to 138% ± 13% (n = 9, p < 0.01), and to 143% ± 72% (n = 8, p < 0.01) when perfused with 10 μM onapristone. Progesterone reduced L-Ca2+ currents to 67% ± 6% (n = 7, p < 0.01) and had no effect with 5 μM nicardipine in bath solution. [Ca2+]i fluorescence was reduced by progesterone to 75% ± 72% (n = 8, p < 0.01). Conclusions: Progesterone decreases the contraction of colonic smooth muscles by enhancing KCa currents and reducing Ca + influx.
KW - Ca activated K (K) channel
KW - Colonic smooth muscle
KW - Contraction
KW - Intracellular calcium
KW - Progesterone
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U2 - 10.1358/mf.2005.27.7.896759
DO - 10.1358/mf.2005.27.7.896759
M3 - Article
C2 - 16258592
AN - SCOPUS:26844535296
SN - 0379-0355
VL - 27
SP - 475
EP - 482
JO - Methods and Findings in Experimental and Clinical Pharmacology
JF - Methods and Findings in Experimental and Clinical Pharmacology
IS - 7
ER -