Experiments were conducted on Myxicola giant axons to determine if the sodium activation and inactivation processes are coupled or independent. The main experimental approach was to examine the effects of changing test pulses on steady-state inactivation curves. Arguments were presented to show that in the presence of a residual uncompensated series resistance the interpretation of the results depends critically on the manner of conducting the experiment. Analytical and numerical calculations were presented to show that as long as test pulses are confined to an approximately linear negative conductance region of the sodium current-voltage characteristic, unambiguous interpretations can be made. When examined in the manner of Hodgkin and Huxley, inactivation in Myxicola is quantitatively similar to that described by the h variable in squid axons. However, when test pulses were increased along the linear negative region of the sodium current-voltage characteristic, steady-state inactivation curves translate to the right along the voltage axis. The shift in the inactivation curve is a linear function of the ratio of the sodium conductance of the test pulses, showing a 5.8 my shift for a twofold increase in conductance. An independent line of evidence indicated that the early rate of development of inactivation is a function of the rise of the sodium conductance.

An analysis of the sodium and potassium conductances of Myxicola giant axons was made in terms of the Hodgkin-Huxley m, n, and h variables. The potassium conductance is proportional to n 2 . In the presence of conditioning hyperpolarization, the delayed current translates to the right along the time axis. When this effect was about saturated, the potassium conductance was proportional to n. The sodium conductance was described by assuming it proportional to mah. There is a range of potentials for which rh and h values fitted to the decay of the sodium conductance may be compared to those determined from the effects of conditioning pulses. Th values determined by the two methods do not agree. A comparison of h, values determined by the two methods indicated that the inactivation of the sodium current is not governed by the Hodgkin-Huxley h variable. Computer simulations show that action potentials, threshold, and subthreshold behavior could be accounted for without reference to data on the effects of initial conditions. However, recovery phenomena (refractoriness, repetitive discharges) could be accounted for only by reference to such data. It was concluded that the sodium conductance is not governed by the product of two independent first order variables.

SYNOPSISThe simplest model for explaining conduction defects in multiple sclerosis (MS) and other demyelinating diseases assumes that the only abnormality present is loss of myelin. A spectrum of physiological abnormalities is seen in MS patients. In addition to apparent slowing and block of conduction (Namerow, 1968a), some fibres are unable faithfully to conduct repetitive impulses and appear to fatigue rapidly (Namerow, 1972). There is also a curious lability whereby clinical signs and symptoms can 152 fluctuate dramatically with small changes in the internal environment. Thus small changes in body temperature produce dramatic reversible alterations in the neurological signs and symptoms of MS, with heat causing a worsening (Nelson and McDowell, 1959;Namerow, 1968b) and cooling an improvement (Watson, 1959). Experimental evidence suggests that this phenomenon is caused by an effect of temperature on conduction in demyelinated axons (Davis, 1970;Davis and Jacobson, 1971;

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