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KMID : 0377220030280010012
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Medical Journal of Chosun Univercity
2003 Volume.28 No. 1 p.12 ~ p.21
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Effects of tamoxifen on the voltage-dependent ionic currents in murine colonic myocytes
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Park Chan-Kuk
Huh Gwang-Sik
Chang Sung-Jong
Kim Man-Woo
Yoon Young
Park Do-Young
Yang Gyong-Chul
Shin Moo-Kyung
Cha Kyung-Hoon
Yeum Cheol-Ho
Yoon Pyung-Jin
Jun Jae-Yeoul
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Abstract
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Background and Objectives : Tamoxifen is a widely used anticancer drug for breast cancer causing frequent gastrointestinal side effects. The change of gastrointestinal motility is associated with the alteration of activities of membrane ion channels. The ion channel is found to play an important role in regulating membrane potential and cell excitability. This study was performed to investigate the effects of tamoxifen on the membrane ionic currents in colonic myocytes.
Materials and Methods : Single colonic myocytes were isolated by using a collganase from murine proximal colon. The membrane currents were recorded by using a whole-cell patch clamp method at room temperature.
Results : Two types of voltage-dependent K+ currents (A-type and delayed rectifier K+ currents) were recorded. Tamoxifen inhibited both types of voltage-dependent K+ currents (10 μM). However, tamoxifen did not change the half-inactivation potential and the recovery time of voltage-dependent K+ currents. Chelerythrine, a protein kinase C inhibitor, and phorbol-12,13-dibutyrate, a protein kinase C activator, did not affect the voltage-dependent K+ currents Guanosine 5-O-2-thiodiphosphate (GDPβS, a G-protein inhibitor), also did not affect on tamoxifen-induced inhibition of voltage-dependent K+ currents. In audition, tamoxifen completely inhibited the voltage-dependent Ca²+ currents in whole-test ranges.
Conclusion : These results suggest that tamoxifen inhibits the voltage-dependent membrane ionic currents in colonic smooth muscle cells, and that this action may be relevant to the gastrointestinal side effects
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KEYWORD
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Colonic myocytes, Tamoxifen, Voltage-dependent K^(+) currents, Voltage-dependent Ca^(2+) currents
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