| Project/Area Number |
05557116
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tohoku University |
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Principal Investigator |
TAIRA Norio Tohoku University, Pharmacology, Professor, 医学部, 教授 (60004553)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Kuniaki Tohoku University, Pharmacology, assistant, 医学部, 助手 (10184459)
NUNOKI Kazuo Tohoku University, Pharmacology, lecture, 医学部, 講師 (10172743)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 1994: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1993: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | antiarrhythmic drugs / cloned K channels / delayd rectifier / transient outward / inward rectifier / 内向き整流電流 |
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| Research Abstract |
1.Voltage-dependent K^+ channels
(1) We investigated the effects of several antiarrhythmic drugs on the currents of rat cardiac Kv1.2 (a delayd rectifier type) and Kv1.4 (a transient type) using the Xenopus oocyte expression system. Unexpectedly relatively pure class III antiarrhythmic drugs, d-sotalol, E-4031 and MS-551, had no effect on the currents of Kv1.2 (I_<Kv1.2>) and Kv1.4 (I_<Kv1.4>) , even though both K^+ channels exist in the heart and class III antiarrhythmic drugs are known to inhibit cardiac K^+ currents. We also investigated whether other antiarrhythmic drugs had any effect on I_<Kv1.2> and I_<Kv1.4>. The drugs studied include disopyramide, quinidine, flecainide, bertosamil, clofilium and verapamil, all of which are known to inhibit native cardiac K^+ currents. All of them except disopyramide inhibited I_<Kv1.2> and I_<Kv1.4> in a concentration-dependent manner, although very high concentrations were required to inhibit them. Some of them inhibited I_<Kv1.2> and I_<Kv1.4> in a time-dependent manner but the other did not. The reason why the antiarrhythmic drugs are less effective on the cloned K^+ channels are remained to be elucidated.
(2) We have cloned a voltage-dependent K^+ channel from rabbit heart. Sequence analysis revealed that it had 85% homology to rat Kv1.5 at the amino acid level. Electrophysiological experiments on the currents of the K^+ channel clone is now under way.
2.Inwardly rectifying K^+ channel
We have cloned an inwardly rectifying K^+ channel from rabbit heart, which we designated RBHIK1. RNA blot analysis revealed the expression of RBHIK1 mRNA in various rabbit tissues especially high level at the ventricular muscle. The effects of several antiarrhythmic drugs on the current of RBHIK1 were investigated. However, the drugs studied so far had no effect on the current of RBHIK1. Further analysis, such as the single channel current analysis of RBHIK1, is currently being carried out.
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