Slow inactivation of the sodium conductance in squid giant axons. Pronase resistance.

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Abstract
Squid giant axons internally perfused with CsF have their Na conductance inactivated due to the low value of the resting potential. When hyperpolarized with voltage clamp to normal values of resting potential, the Na conductance recovers with an exponential time course. The time constant of recovery is of the order of 30 sec at a membrane potential of -70 mV and at 5.degree. C. The recovery from slow inactivation has a Q10 of about 3. The development of inactivation during depolarization is slow. The time constant varies between 10-20 s at 5.degree. C, depending upon the value of the membrane potential. Slow inactivation is observed in NaF perfused axons and in intact axons with a low resting potential. Although internal perfusion with pronase (or a purified fraction of this enzymic complex) blocks the fast (h) inactivation of the Na conductance, the slow inactivation remains. The recovery is similar before and after the proteolytic treatment. Slow inactivation appears to develop faster after enzymic perfusion. Slow inactivation develops without any apparent change in distributed or local membrane surface charge. Slow inactivation is probably a general property of Na conductance as in many other conductance channels in excitable membranes. It is probably a phenomenon independent of fast inactivation, and pronase could somehow accelerate its onset. An alternative model, in which slow inactivation is coupled to fast inactivation, is proposed. This model is consistent with the results presented and is very similar to one proposed to explain the frequency response of the Na currents in Myxicola giant axons (Rudy, 1975, 1978).