Effects of fatty acids on membrane currents in the squid giant axon

The effects of fatty acids on the ionic currents of the voltage-clamped squid giant axon were investigated using intracellular and extracellular application of the test substances. Fatty acids mainly suppress the Na current but have little effect on the K current. These effects are completely reversed after washing with control solution. The concentrations required to suppress the peak inward current by 50% and Hill number were determined for each fatty acid. ED50 decreased about 1/3 for each increase of one carbon atom. The standard free energy was -3.05 kJ mole-1 for CH2. The Hill number was 1.58 for 2-decenoic acid. The suppression effect of the fatty acids depends on the number of carbon atoms in the compounds and their chemical structure. Suppression of the Na current was clearly observed when the number of carbon atoms exceeded eight. When fatty acids of the same chain length were compared, 2-decenoic acid had strong inhibitory activity, but sebacic acid had no effect at all on the Na channel. The currents were fitted to equations similar to those proposed by Hodgkin and Huxley (J. Physiol. (London) 117:500-544, 1952) and the changes in the parameters of these equations in the presence of fatty acids were calculated. The curve of the steady-state activation parameter (m infinity) for the Na current against membrane potential and the time constant of activation (tau m) were shifted 20 mV in a depolarizing direction by the application of fatty acids. The time constant for inactivation (tau h) was almost no change by application of the fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)