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These sodium channel mutants, expressed in <jats:italic>Xenopus<\/jats:italic> oocytes by microinjection of cDNA\u2010derived mRNAs, were tested for sensitivity to tetrodotoxin and saxitoxin and for single\u2010channel conductance. The results obtained show that mutations involving 2 clusters of predominantly negatively charged residues, located at equivalent positions in the SS2 segment of the 4 repeats, strongly reduce toxin sensitivity, whereas mutations of adjacent residues exert much smaller or no effects. This suggests that the 2 clusters of residues, probably forming ring structures, take part in the extracellular mouth and\/or the pore wall of the sodium channel. This view is further supported by our finding that all mutations reducing net negative charge in these amino acid clusters cause a marked decrease in single\u2010channel conductance.<\/jats:p>","DOI":"10.1016\/0014-5793(91)81159-6","type":"journal-article","created":{"date-parts":[[2002,7,25]],"date-time":"2002-07-25T09:09:11Z","timestamp":1027588151000},"page":"93-96","source":"Crossref","is-referenced-by-count":370,"title":["Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II"],"prefix":"10.1002","volume":"293","author":[{"given":"Heinrich","family":"Terlau","sequence":"first","affiliation":[]},{"given":"Stefan H.","family":"Heinemann","sequence":"additional","affiliation":[]},{"given":"Walter","family":"St\u00fchmer","sequence":"additional","affiliation":[]},{"given":"Michael","family":"Pusch","sequence":"additional","affiliation":[]},{"given":"Franco","family":"Conti","sequence":"additional","affiliation":[]},{"given":"Keiji","family":"Imoto","sequence":"additional","affiliation":[]},{"given":"Shosaku","family":"Numa","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2002,1,16]]},"reference":[{"key":"e_1_2_1_2_1","unstructured":"1984 Sinauer Sunderland MA B. 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