| Project/Area Number |
10671545
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Hiroshima University |
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Principal Investigator |
MIVOSHI Hiroshi HIROSHIMA UNIVERSITY, MEDICAL HOSPITAL, 医学部・附属病院, 助手 (40294590)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | pregnancy / uterine smooth muscle / parturition / preterm delivery / patch clamp / electrophysiology / potassium channel / ion channel / 子宮収縮 / パッチクランプ / 陣痛 / キャップ結合 / ギャップ結合 |
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| Research Abstract |
Potassium (K) currents in uterine smooth muscle cells play important roles in regulating contractility by controlling the resting membrane potential. We applied the patch clamp method to myometrial cells isolated from pregnant rat for characterization of K channel.
In whole-cell method, two components of voltage-dependent K current, delayed rectifier (Kd) and transient (Kt) were observed. Kd currents have a slow inactivation process (τ>500ms) and a half-inactivation voltage (V_<1/2>) of -47 mV.Kt currents inactivated more quickly (τ<50ms) with V_<1/2>=-71 mV.The Kd current is sensitive to tetraethylammonium (TEA, IC_<50> of 5.0 mM) and indapamide but not to E-4031, indicating this channel is IKs type. This channel should reporalize the membrane potential after action potentials. Kt channel is sensitive to 4AP (2 mM) and may inhibit the generation of action potentials. In inside-out mode, large Kca channels (250 pS) were observed with an IC_<50> for intracellular Ca^<2+> of 3×10^<-6> M and detected to be maxi-K type. It is clear that Kd current is not due to Kca since 1) In inside-out mode, Kca current is very sensitive to ChTX (charybdotoxin, IC_<50>=20 nM), but in whole cell mode, 100 nM ChTX blocked Kd current by just 15%. 2) TEA was much more effective in blocking Kca than Kd. 3) Kd current was observed with 5 mM BAPTA in the intracellular solution (Ca<10^<-8>). The role of this channel should be hyperpolarization after the uterine contraction.
We conclude that there are at least two types of voltage dependent K channels in addition to a Ca-activated K channel (maxi-K type) in myometrial cells. These studies contribute to an understanding of current regulation in the myometrial cell and may assist in defining strategies for the control of myometrial contractility.
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