Blocking and modifying actions of octanol on Na channels in frog myelinated nerve.
The actions of externally applied n-octanol on Na channels in myelinated frog nerve fibres were studied under voltage clamp conditions. Upon octanol application peak Na inward currents declined in two phases: 90% of the reduction occurred in less than 2 min but a steady-state was reached only after 15 min. During washout the currents came to a stable level within 10 min. The reduction of Na inward currents by octanol was dependent on the amplitude and duration of prepotentials. At the resting potential (VH = 0 mV) 0.4 mM octanol reduced peak Na inward currents at V = 60 mV by 50%. After a prepulse of -60 mV and 50 ms duration Na currents decreased only by 20%. At a hyperpolarizing holding potential of VH = -28 mV 0.7 mM octanol reduced peak inward Na currents to one half. Octanol depressed Na currents at all potentials by approximately the same factor. The Na reversal potential VNa remained unchanged. 0.7 mM external octanol shifted the Na activation curve m infinity (V) by 5 mV to more positive and the inactivation curve h infinity (V) by 14 mV to more negative potentials. The midpoint slopes of both curves were reduced. The time constants of Na activation and inactivation at small depolarizations were decreased. The conductance gamma of a single Na channel and the number No of conducting Na channels per node were determined from nonstationary Na current fluctuations. 0.7 mM octanol increased gamma by a factor of 1.6 and reduced No by a factor of 0.34. It is concluded that octanol blocks some Na channels and modifies the remaining unblocked channels.
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D000818:Animals; D004553:Electric Conductivity; D007473:Ion Channels / Q000032:analysis / Q000187:drug effects*; D007700:Kinetics; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism*; D000442:Octanols / Q000494:pharmacology*; D011893:Rana esculenta; D012964:Sodium / Q000378:metabolism*
D007473:Ion Channels; D000442:Octanols; D012964:Sodium