1987 Fiscal Year Final Research Report Summary
Mechanisms of action of cardiotonic polypeptide marine toxins on sodium channels
| Project/Area Number |
61480117
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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 |
General pharmacology
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| Research Institution | Kyoto University |
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Principal Investigator |
FUJIWARA Motohatsu Kyoto University, Faculty of Medicine Professor, 医学部, 教授 (90025536)
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| Co-Investigator(Kenkyū-buntansha) |
MURAMATSU Ikunobu Fukui Medical School Associate Professor (Higuchi,Masa), 医学部, 助教授 (10111965)
HATANAKA Shoichi Kyoto University, Institute of Virus Professor, ウィルス研究所, 教授 (30142300)
TANIGUCHI Takashi Kyoto University, Faculty of Medicine Lecturer, 医学部, 講師 (10111957)
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| Project Period (FY) |
1986 – 1987
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| Keywords | Cardiotonic marine toxins / Goniopora toxin / palytoxin / positive inotropic action / Prolongation of action potential / Sodium channel / Inactivation process / cDNAのクローニング |
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| Research Abstract |
Mechanisms of action of two cardiotonic marine toxins, goniopora toxin and palytoxin, were studies and then compared with other marine toxins. 1) Goniopora toxin (GPT), a polypeptide toxin of 9,700 Da isolated from coral Goniopora spp., produced a potent positive inotropic action on cardiac muscles and increased the transmitter release evoked by electrical stimulation. These action were closely associated with the prolongation of actio potential. Voltage clamp experiments using guinea-pig ventricular myocytes and mouse neuroblastoma cells revealed that GPT selectively acted on the sodium channel, resulting in an inhibition of the inactivation process and that the effects of GPT were voltage-, time- and cation-dependent. The binding site of GPT in the sodium channel is different from that of peptide toxins isolated from scorpion and sea anemone. 2) GPT is composed of 88 amino acid residues containing 10 half-cystinyl residues. There is no homology of primary structure between GPT and other peptide toxins mentioned above. 3) Palytoxin (PTX), isolated from the zoanthid Palythoa species, depolarized the guinea-pig ventricular myocytes in a sodium-dependent but tetrodotoxin-resistant manner. Cell-attached patch clamp experiments showed that PTX induced a new type of channel with unique ionic selectivity and gating behavior different from those of the existing sodium channels.
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