Mechanism underlying diuretic-induced enhancement of KィイD1+ィエD1 excretion
| Project/Area Number |
10670095
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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 |
General pharmacology
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| Research Institution | Jichi Medical School |
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Principal Investigator |
TANIGUCHI Junichi Jichi Medical School, Faculty of Medicine, Instructor, 医学部, 講師 (90179838)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | diuretic / connecting tubule / flow-dependence / potassium excretion / hypokalemia / maxi KィイD1+ィエD1 channel / Kir1.1 / low conductance KィイD1+ィエD1 channel / 流速依存性 / Kir1.1 / マキシK^+チャネル / ROMKチャネル |
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| Research Abstract |
Diuretics augment KィイD1+ィエD1 which sometimes cause hypokalemia, because the diuretic-induced increase of luminal flow enhances flow-dependent KィイD1+ィエD1 secretion in distal nephron. In order to clarify the mechanism of flow-dependent KィイD1+ィエD1 secretion, Single channel currents were recorded from the luminal membrane of an everted rabbit connecting tubule with patch clamp technique. In cell-attached patch clamp studies, CaィイD12+ィエD1-activated maxi KィイD1+ィエD1 channels (280pS) found in this membrane showed little open probability compared with that of small conductance KィイD1+ィエD1 channels (35pS), although they were activated by stretching path membrane. The maxi KィイD1+ィエD1 channels were not totally blocked with 1μM charybdotoxin, but not with 33μM arachidonic acid. The small conductance KィイD1+ィエD1 channels, vice versa. Luminal KィイD1+ィエD1 conductance in the connecting tubule perfused, in vitro, was estimated from the deflection of transepithelial voltage (ΔVィイD1tィエD1), when luminal KィイD1+ィエD1 concentration was increased from 5 to 15mEq, by adding 10mM K gluconate. The luminal KィイD1+ィエD1 was increased flow-dependently and was blocked with luminally applied 1μM charybdotoxin. The 33mM arachidonic acid applied into lumen showed no effect on the luminal KィイD1+ィエD1 conductance estimated above. These observations suggest that the activation of maxi KィイD1+ィエD1 channels coupled with stretch-activation of Ca-permeable nonselective cation channels found in the same membrane play a dominat role in flow-dependent KィイD1+ィエD1secretion. It is likely that an increased luminal flow induced by an application of diuretic stimulates the coupling between stretch-activated cation channels and maxi KィイD1+ィエD1 and that KィイD1+ィエD1 secreted via the maxi KィイD1+ィエD1 in the rabbit connecting tubules.
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Report
(3 results)
Research Products
(10 results)
