Abstract
Pompilidotoxins (PMTXs), derived from the venom of solitary wasp has been known to facilitate synaptic transmission in the lobster neuromuscular junction, and a recent further study from rat trigeminal neurons revealed that the toxin slows Na+ channel inactivation without modifying activation process. Here we report that β-PMTX modifies rat brain type II Na+ channel α-subunit (rBII) expressed in human embryonic kidney cells but fails to act on the rat heart α-subunit (rH1) at similar concentrations. We constructed a series of chimeric mutants of rBII and rH1 Na+ channels and compared modification of the steady-state Na+ currents by β-PMTX. We found that a difference in a single amino acid between Glu-1616 in rBII and Gln-1615 in rH1 at the extracellular loop of D4S3-S4 is crucial for the action of β-PMTX. PMTXs, which are small peptides with 13 amino acids, would be a potential tool for exploring a new functional moiety of Na+channels.
Footnotes
- Received August 21, 2000.
- Accepted February 27, 2001.
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Send reprint requests to: Dr. Issei Seyama, Department of Physiology, School of Medicine, Hiroshima University, Kasumi 1–2-3, Hiroshima 734-8551, Japan. E-mail:issei{at}mcai.med.hiroshima-u.ac.jp
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This work was supported by Grants from the Ministry of Education and Culture of Japan to K.Y. (11470011) and E.K. (11770023); by the research grant for cardiovascular diseases from the Ministry of Health and Welfare to I.S. (11C-1); by Special Coordination Funds for Promoting Science and Technology of the STA of the Japanese Government to N.K.; by grant-in-aid for Scientific Research (12470483) from the Ministry of Education, Science, Sports and Culture of Japan; and a grant from Core Research for Evolutionary Science and Technology of Japan Science and Technology Corporation to H.N.
- The American Society for Pharmacology and Experimental Therapeutics
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