| Project/Area Number |
11670663
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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 |
Circulatory organs internal medicine
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| Research Institution | Tokyo medical and Dental University |
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Principal Investigator |
HIRANO Yuji Department of Cardiovascular Diseases, Medical Research Institute, Tokyo medical and Dental University Associate Professor, 難治疾患研究所, 助教授 (00181181)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Na channel / ionic selectivity / Ca^<2+> ion / slip-mode conductance / voltage-dependent block / isoproterenol / veratridine |
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| Research Abstract |
The possibility of Ca^<2+> permeation through cardiac Na channels ("slip mode conductance") was explorerd through the analysis of voltage dependent block of Na channels by Ca^<2+>. Ca^<2+> block of Na channels was evident in rat and guinea-pig ventricular myocytes during cell-attached single channel recording with physiological ionic environment (140mM-Na^+ and 1 to 10mM-Ca^<2+> in the pipette solution). Increasing external Ca^<2+> concentration ([Ca^<2+>]_0) in the pipette solution reduced the unitary current amplitude predominantly at negative potentials. With [Ca^<2+>]_0>1mM, unitary current amplitude did not increase at potentials negative to -40mV in spite of augmented driving forces. Application of 5μM-isoproterenol potentiated the single channel activity elicited by depolarizing pulses from the holding potential of-120mV, indicating that the channels in the patch under examination were modified by protein kinase A (PKA) stimulation. Increased activity was also confirmed with veratridine-modified Na channels, where channel openings were markedly prolonged. In either case, isoproterenol-induced potentiation did not reduce nor alter the properties of Ca^<2+> block of cardiac Na channels, as evidenced by the stable unitary current amplitudes at potential levels between -20 and -60mV.These results indicate that interactions among Na^+, Ca^<2+> and the channel molecule were not modified with respect to permeation properties. They therefore argue against "slip mode" concept of classical cardiac Na channel, if a general concept of ion permeation through "multi-ion pores" is applicable to determine the ionic selectivity of Na channels.
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