ISSN:
1432-2013
Keywords:
Batrachotoxin Na+ channel S6 segments Sea anemone toxin Veratridine
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract. Biochemical evidence indicates that veratridine (VTD) and batrachotoxin (BTX) share a common binding site in Na+ channels. Under whole-cell voltage-clamp conditions, we examined this single receptor hypothesis by studying the VTD phenotype in BTX-resistant muscle Na+ channels, µ1-I433K, N434K, L437K, F1579K, and N1584K. Derived from point mutations at segments D1–S6 and D4–S6, these mutant Na+ channels are resistant to 5 µM BTX when expressed in human embryonic kidney cells. In contrast to the wild-type phenotype, VTD at 200 µM elicits little or no maintained current during a test pulse at +50 mV, and little or no "tail" current after the test pulse in all BTX-resistant mutant channels. Paradoxically, VTD retains its ability to inhibit the peak Na+ current in BTX-resistant mutant Na+ channels. To explain these mutant phenotypes, we propose a two-step binding reaction scheme. An initial VTD-binding interaction with the Na+ channel results in the inhibition of peak current amplitude, and a second binding reaction results in the trapping of VTD within the D1–S6 and D4–S6 domain interface. The failure of BTX-resistant mutant Na+ channels to trap VTD suggests that segments of D1–S6 and D4–S6 form a common receptor for VTD and BTX.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004249900229
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