Sodium inactivation

Khodorov BI. Sodium inactivation and drug-induced immobilization of the gating charge in nerve membrane. Prog Biophys Mol Biol 1981 37 49-89. 

Fig. 6C shows that, when the sodium inactivation curve is shifted by 10 mV towards more positive potentials to account for the properties of some regions of the axons such as the site of initiation of the nerve impulse, the equations predict that the same small insecticide concentration that would normally only increase the afterpotential (lower trace) induces repetitive activity (upper trace). 

Fig.6 Computer reconstruction of nerve membrane activity based on the existence in the membrane of a small proportion (A) of modified sodium channels. In panels A and B, this proportion was varied from zero to 0.048 (i.e. 4.8 % of modified channels) to reproduce the membrane potential changes observed in strongly poisoned insects. In panel C, repetitive firing was obtained by shifting the sodium inactivation curve towards more positive potentials. Tau p x 200 indicates that, for these examples, the time constant of activation of the modified channels was 100 times slower than that of the normal channels.

Ju YK, Saint DA, Gage PW (1992) Effects of lignocaine and quinidine on the persistent sodium current in rat ventricular myocytes. Br J Pharmacol 107 311-316 Khodorov B, Shishkove L, Peganov E, Revenko S (1976) Inhibition of sodium currents in frog Ranvier node treated with local anesthetics. Role of slow sodium inactivation. Biochim Biophys Acta 433 409-435... 

The spectral analysis of fluctuations yields also valuable information, and it can be used to test the validity of kinetic schemes describing the transitions between different channel states. In Ranvier nodes the component of the sodium current fluctuations which corresponds to the sodium inactivation process observed in voltage-clamp experiments is much larger than expected from a simple Hodgkin-Huxley scheme with statistically independent activation and inactivation processes. This finding provides a strong argument in favour of the hypothesis that the inactivation process is at least partially sequential to the activation process. 

True random fluctuations with zero mean were extracted from the measured signals by subtracting the systematic drifts. The power spectra of the resulting records are identical to those obtained in previous works (14,15) above 100 Hz, but they provide reliable information also in the range of 3 to 100 Hz were they show the tendency to reach the low frequency plateau expected from a simple Lorentzian behaviour. In this case no significant 1/f noise contributions were observed, and the measured spectra could be fitted by the superposition of a simple Lorentzian noise, L(f,X] ) associated with the time constant of sodium inactivation, and a pseudo-... 

Conductance of the sodium channel in myelinated nerve fibres with modified sodium inactivation. J.Physiol. 262 729-742. 

A small, reproducible effect of pressure on the sodium inactivation curve, h (E), was observed. For P=612 atm the voltage yielding 50% inactivation was shifted by about 2 mV in the hyperpolarizing direction and the steepness of the h (E) curve at the midpoint was decreased by about 26%. 

Another important conclusion gleaned from our data bears on the question of the effect of pressure on the kinetics of sodium inactivation. Henderson Gilbert (7) reported no significant modification of T, by pressure, whereas they estimated activation volumes of 30 to Id cm /mole from changes of This finding would provide very... 

Prolonged subthreshold stimuli can produce the phenomenon of accommodation. A long-duration cathodic pulse to mammalian axon that produces subthreshold depolarization will increase sodium inactivation, reducing the number of axons that can be recruited and so increasing the threshold. This is not a problem with brief pulses that are shorter than the time constant of sodium channel inactivation, but can be with more prolonged pulses. 

Neumcke, B., W. Schwarz, and R. Stampfli Modification of Sodium Inactivation in Myelinated Nerve by Anemonia Toxin II and lodate. Analysis of Current Fluctuations and Current Relaxations. Biochim. Biophys. Acta 600, 456 (1980). 

Warashina, A., and S. Fujita Effect of Sea Anemone Toxin on the Sodium Inactivation Process in Crayfish Axons. J. Gen. Physiol. 81, 305 (1983). 

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