1988 Fiscal Year Final Research Report Summary
Study of the outward current systems of mammalian ventricular muscle cells in relation to the genesis of rhythm disturbances
| Project/Area Number |
62480214
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Tokyo Medical and Dental University, Medical Research Institute |
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Principal Investigator |
HIRAOKA Masayasu Medical Research Instite, Tokyo Medical and Dental University, Professor, 難治疾患研究所, 教授 (80014281)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Single ventricular myocyte / Patch clamp method / Transient outward current / Inactivation process / 心室再分極相 |
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| Research Abstract |
The properties and functional roles of the transient outward current in mammalian ventricular muscle cells were studied using the patch clamp technique applied to isolated rabbit ventricular myocytes. The transient outward current (I_<to>) has been assumed to be a unique Property of purkinje cells but not to be present or underdeveloped in ventricular cells. In this study, we demonstrated the presence of I_<to> in rabbit ventricular myocytes when depolarization was applied from the holding potential at -60 mV or more negative to voltages positive to -20 mV. The current was shown to contribute to the formation of small phase l and notch on ventricular action potentials.
This I_<to> was activated even after blocking the Ca^<2+> current, indicating this I_<to> as Ca^<++>-insensitive one. The current exhibited a slow recovery kinetics showing the time constant around 2 sec. Because of this slow recovery kinetics of I_<to>, premature excitations with short coupling intervals showed augmented
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plateau and prolonged action potential duration, in the face of the rapid recovering the Ca^<2+> current.The voltage- and time-dependent activation and inactivation, and their kinetics were fully analyzed.The charge carrier of this I_<to> was mainly K^+ and partly Na^+. This I_<to> component was easily blocked by 4-aminopyridine (4-AP).
There was another type of I_<to> which was sensitive to 4-AP but was blocked by caffeine. The caffeine-sensitive I_<to> had faster kinetics than those of Ca^<2+>-insensitive I_<to> and increased with rapid pulsations. The current was abolished by intracellular EGTA, and by external application of ryanodine or Sr^<2+> for Ca^<2+>. These results indicate the current as Ca^<2+>-sensitive I_<to>. The Ca^<2+>-sensitive I_<to> contributes to ventricular repolarization at fast heart rate, whereas the Ca^<2+>-insensitive one to show heart rate. The Ca^<2+>-sensitive and -insensitive I_<to> together with the Ca^<2+> current were shown to contribute to the action potential alterations when the heart rate was suddenly increased or a rapid stimulation was initiated after a rest. The single channel recording of this Ca^<2+>-sensitive I_<to> for the further deliveation of its properties has not been succeeded and the study is currently undertaken. Less
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