Interactions between a pore-blocking peptide and the voltage sensor of the sodium channel: an electrostatic approach to channel geometry.
Few experimental data illuminate the relationship between the molecular structures that mediate ion conduction through voltage-dependent ion channels and the structures responsible for sensing transmembrane voltage and controlling gating. To fill this void, we have used a strongly cationic, mutated mu-conotoxin peptide, which only partially blocks current through voltage-dependent sodium channels, to study voltage-dependent activation gating in both bound and unbound channels. When the peptide binds to the ion-conducting pore, it inhibit channel opening, necessitating stronger depolarization for channel activation. We show that this activation shift could result entirely from electrostatic inhibition of the movement of the voltage-sensing S4 charges and estimate the approximate physical distance through which the S4 charges move.
French
R J
RJ
Department of Medical Physiology, Faculty of Medicine, University of Calgary, Alberta, Canada.
Prusak-Sochaczewski
E
E
Zamponi
G W
GW
Becker
S
S
Kularatna
A S
AS
Horn
R
R
D000818:Animals; D001496:Batrachotoxins / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004048:Diethylamines / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology; D008433:Mathematics; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology*
D001496:Batrachotoxins; D004048:Diethylamines; D010456:Peptides, Cyclic; C102513:R13Q; D015222:Sodium Channels; D018999:Charybdotoxin; C034281:diethylamine; D002118:Calcium