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A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid‐sensitive channel in sensory neurons
Author(s) -
Diochot Sylvie,
Baron Anne,
Rash Lachlan D,
Deval Emmanuel,
Escoubas Pierre,
Scarzello Sabine,
Salinas Miguel,
Lazdunski Michel
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600177
Subject(s) - art , humanities , library science , art history , computer science
From a systematic screening of animal venoms, we isolated a new toxin (APETx2) from the sea anemone Anthopleura elegantissima , which inhibits ASIC3 homomeric channels and ASIC3‐containing heteromeric channels both in heterologous expression systems and in primary cultures of rat sensory neurons. APETx2 is a 42 amino‐acid peptide crosslinked by three disulfide bridges, with a structural organization similar to that of other sea anemone toxins that inhibit voltage‐sensitive Na + and K + channels. APETx2 reversibly inhibits rat ASIC3 (IC 50 =63 nM), without any effect on ASIC1a, ASIC1b, and ASIC2a. APETx2 directly inhibits the ASIC3 channel by acting at its external side, and it does not modify the channel unitary conductance. APETx2 also inhibits heteromeric ASIC2b+3 current (IC 50 =117 nM), while it has less affinity for ASIC1b+3 (IC 50 =0.9 μM), ASIC1a+3 (IC 50 =2 μM), and no effect on the ASIC2a+3 current. The ASIC3‐like current in primary cultured sensory neurons is partly and reversibly inhibited by APETx2 with an IC 50 of 216 nM, probably due to the mixed inhibitions of various co‐expressed ASIC3‐containing channels.