The asymmetrical effects of some ionized n‐octyl derivatives on the sodium current of the giant axon of Loligo forbesi.

Abstract

The effects of octyltrimethylammonium ions (OTMA+), octyl sulfate ions (OS-) and octanoic acid (OA) on the Na current of the voltage-clamped squid giant axon were investigated using intracellular and extracellular application of the test substances. OTMA+ applied externally at concentrations of 0.8-5.0 mM produces a small reversible increase in the peak inward Na current in both intact and CsF-perfused axons. Intracellular application of OTMA+ at 0.8 mM to CsF-perfused axons causes a reversible 50% suppression of peak inward Na- current. The inhibition of peak inward current by internal OTMA+ arises largely from a shift of the steady-state activation parameter (n.infin.) in the depolarizing direction along the voltage axis. There is little use dependence of the current suppression by OTMA+. OA applied either internally or externally is more effective at suppressing peak inward Na current at pH 6.0 than at pH 7.4. At pH 6.0 external application of 5 mM-OA to perfused axons causes .apprx. 60% suppression. This is associated with a depolarizing shift of m.infin. of about 13 mV and a hyperpolarizing shift of the steady-state inactivation (h.infin.) curve of about 4 mV. The effects of internal and external OA are broadly similar except that the h.infin. shift is not seen with internal application. OS- at concentrations above 2.0 mM produces complete irreversible loss of Na current. At 2.0 mM, OS- produces 10% current suppression and a small depolarizing shift of the m.infin. curve. Internal and external applications of OS- differ little except that external OS- causes a 25% increase in the time constant of activation (.tau.m). The possible origins of these effects are discussed. The shift of m.infin. caused by internal OTMA+ may be due to a diminution of the lipid dipole potential at the internal surface of the membrane caused by OTMA+ adsorption. This effect could also account for the m.infin. shift caused by OA. The results showing that OA produces shifts of opposite sign in the voltage dependence of m.infin. and h.infin. are discussed with respect to their implications for models of Na channel gating.