Kinetic properties of single sodium channels modified by fenvalerate in mouse neuroblastoma cells.
(1) The kinetic properties of single sodium channels modified by the pyrethroid fenvalerate have been analyzed by patch clamp techniques using the cultured mouse neuroblastoma cells. (2) Fenvalerate drastically prolonged the open time of single sodium channels from the normal value of 5 ms to several hundred milliseconds during a depolarizing pulse. The channels remained open after termination of a depolarizing pulse for as long as several seconds. (3) The channel lifetime varied with the membrane potential, attained a maximum at -70 mV, and decreased with hyperpolarization and depolarization from -70 mV. (4) Prolonged openings of the modified channels allowed a current-voltage curve for a single channel to be plotted by sweeping a ramp pulse. The single channel conductance had a value of 11 pS and was linear over potentials ranging from 0 to -100 mV. (5) Power density spectral analysis of the open channel current noise indicated a single Lorentzian curve with a cut-off frequency at 90 Hz, indicating that the increase in noise during channel opening resulted from a relatively slow kinetic process. (6) The probability of the channel being modified by fenvalerate was independent of the length of time during which the channel was opened. This observation suggests that channel modification had taken place before the channel opened. This study of the prolonged opening at the single channel level provides a new insight into open channel properties and the kinetics of channel modification.
Holloway
S F
SF
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
Salgado
V L
VL
Wu
C H
CH
Narahashi
T
T
D000818:Animals; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma; D009570:Nitriles; D011722:Pyrethrins / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D009570:Nitriles; D011722:Pyrethrins; D015222:Sodium Channels; C017690:fenvalerate