Comparison of ionic selectivity of batrachotoxin-activated channels with different tetrodotoxin dissociation constants

Li Yen Mae Huang, William A. Catterall, Gerald Ehrenstein

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Abstract

The purpose of these experiments is to test whether the differences between normal and tetrodotoxin-resistant Na+ channels reside in the selectivity filter. To do this, we have compared the selectivity of batrachotoxin-activated channels for alkali cations, organic cations, and nonelectrolytes in two neuroblastoma clonal cell lines: N18, which has normal tetrodotoxin (TTX) sensitivity, and C9, which is relatively TTX-resistant. We have also studied the effect of H+ on Na+ permeability and on the interaction between TTX and its receptor site in both cell lines. There is no qualitative difference between the two cell lines in any of these properties. In both cell lines the batrachotoxin-activated Na+ channels have a selectivity sequence of Tl+ > Na+ > K+, guanidinium > Rb+ > Cs+, methylamine. Also, in both cell lines H+ blocks Na+ channels with a pK a of 5.5 and inhibits the action of TTX with the same pK a. These observations indicate that the selectivity filters of the Na+ channels in C9 and N18 do not differ significantly despite the 100-fold difference in TTX-affinity. Our selectivity studies of batrachotoxinactivated Na+ channels for both cell lines suggest that these toxin-activated Na+ channels have a limiting pore size of 3.8 × 6.0Å, as compared to a pore size of 3.0 × 5.0 Å for potential-activated Na+ channels.

Original languageEnglish (US)
Pages (from-to)839-854
Number of pages16
JournalJournal of General Physiology
Volume73
Issue number6
DOIs
StatePublished - Jun 1 1979
Externally publishedYes

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ASJC Scopus subject areas

  • Physiology

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