생쥐 대장 평활근에서 막전압-의존성 이온 전류에 대한 tamoxifen 효과 = Effects of tamoxifen on the voltage-dependent ionic currents in murine colonic myocytes

다국어 초록 (Multilingual Abstract)

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

목차 (Table of Contents)

• 서 론
• 재료 및 방법
• 1. 세포분리
• 2. 막전류의 기록
• 3. 실험용액
• 4. 실험에 사용된 약물
• 결과
• 1. 막전압-의존성 칼륨 전류
• 2. 막전압 -의존성 칼륨 전류에 대한 tamoxifen의 효과
• 3. 막전압 -의존성 칼륨 전류에 대한 protein kinase C의 역할
• 4. 막전압-의존성 칼슘 전류에 대한 tamoxifen의 효과
• 고 찰
• 결 론