Current-dependent inactivation induced by sodium depletion in normal and batrachotoxin-treated frog node of Ranvier

In batrachotoxin (BTX)-treated frog node of Ranvier, in spite of a marked reduction in Na inactivation, the Na current still presents a time- and voltage-dependent inactivation that could induce a 50-60% decrease in the current. The inactivation was found to be modified by changing the amplitude of a conditioning pulse, adding tetrodotoxin in the external solution, or replacing NaCl with KCl in the external solution. Conditioning pulses were able to alter the reversal potential of the BTX-modified Na current (Vrev). Vrev was shifted toward negative values for inward conditioning currents and was shifted toward positive values for outward conditioning currents. The change in Vrev was proportional to the conditioning current amplitude. Large inward currents induced 15-25 mV shifts of Vrev. During a 10-20-ms depolarizing pulse, the inactivation and change in Vrev were proportional to the time integral of the current. For longer depolarizations, Vrev reached a steady state level proportional to the current amplitude. The conductance, as calculated from the current and the actual Vrev, showed an inactivation proportional to exp(Vrev F/RT). These observations suggest that the BTX-modified Na current induces a decrease in local Na concentrations, which results in an alteration of the driving force and the conductance. During a pulse that induced a large inward current, the Na space concentration [( Na]s) changed from 114 to 50-60 mM. In normal fibers, the reversal potential of Na current was also shifted toward negative values by a prepulse that induced a large inward current. The change in Vrev reached 5-15 mV, which corresponded to a decrease in [Na]s of 20-50 mM. This change in Vrev slightly altered the time course of Na current. On the basis of a three-compartment model (axoplasm-perinodal space-bulk solution), a Na permeability of the barrier between the space and the bulk solution (PNa,s) and a mean thickness of the space (theta) were calculated. The mean value of PNa,s was 0.0051 cm X s-1 in both normal and BTX-treated fibers, whereas the value of theta was 0.29 micron in BTX-treated fibers and 0.05 micron in normal fibers. When compared with the values calculated during K accumulation, PNa,s was 10 times smaller than PK,s and theta Na-BTX was equal to theta K.(ABSTRACT TRUNCATED AT 400 WORDS)