For myelinated fibers, it is experimentally well established that spike conduction velocity is proportional to fiber diameter. However no really satisfactory theoretical treatment has been proposed. To treat this problem a theoretical axon was described consisting of lengths of passive leaky cable (internode) regularly interrupted by short isopotential patches of excitable membrane (node). The nodal membrane was assumed to obey the Frankenhaeuser-Huxley equations. The explicit diameter dependencies of the various parameters were incorporated into the equations. The fiber diameter to axon diameter ratio was taken to be constant, and the internode length was taken to be proportional to the fiber diameter. Both these conditions reflect the situation that exists in real, experimental fibers. Dimensional analysis shows that these anatomical conditions are equivalent to Rushton's (1951) assumption of corresponding states. Hence, conduction velocity will be proportional to fiber diameter, in complete agreement with the experimental findings. Digital computer solutions of these equations were made in order to compute a set of actual velocities. Computations made with constant internode length or constant myelin thickness (i.e., nonconstant fiber diameter to axon diameter ratio) did not show linearity of the velocity-diameter relation.

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.

Whole‐cell patch clamp currents from freshly isolated adult rat ventricular cells, recorded in external Ca2+ (Ca2+o) but no external Na+ (Ma4o), displayed two inward current components: a smaller component that activated over more negative potentials and a larger component (L‐type Ca2+ current) that activated at more positive potentials. The smaller component was not generated by Ca2+ channels. It was insensitive to 50 μm M2+ and 10 μm La3+, but suppressed by 10 μm tetrodotoxin (TTX). We refer to this component as ICa(TTx). The conductance–voltage, g(V), relation in Ca2+o only was well described by a single Boltzmann function (half‐maximum potential, V½, of –44.5; slope factor, k, of –4.49 mV, means of 3 cells). g(V) in Ca2+o plus Na4o was better described as the sum of two Boltzmann functions, one nearly identical to that in Ca2+o only (mean V½ of –45.1 and k of – 3.90 mV), and one clearly distinct (mean V½ of –35.6 and k of –2.31 mV). Mean maximum conductance for ICa(TTX) channels increased 23.7 % on adding 1 mm Na+o to 3 mm Ca2+o. ICa(TTx) channels are permeable to Na+ ions, insensitive to Ni2+ and La3+ and blocked by TTX. They are Na+ channels. I Ca(TTx) channels are distinct from classical cardiac Na+ channels. They activate and inactivate over a more negative range of potentials and have a slower time constant of inactivation than the classical Na+ channels. They are also distinct from yet another rat ventricular Na+ current component characterized by a much higher TTX sensitivity and by a persistent, non‐fast‐inactivating fraction. That ICa(TTx) channels activate over a more negative range of potentials than classical cardiac Na+ channels suggests that they may be critical for triggering the ventricular action potential and so of importance for cardiac arrhythmias.

A lB, S T R A C T The time-course of the decay of INa on resetting the membrane potential to various levels after test steps in potential was studied. The effects of different initial conditions on these Na tail currents were also studied. For postpulse potentials at or negative to -35 mV, these currents may be attributed nearly entirely to the shutdown of the activation process, inactivation being little involved. Several relaxations may be detected in the tail currents. The slower two are well defined exponentials with time constants of ~ 1 ms and 100 V.s in the hyperpolarizing potential range. The fastest relaxation is only poorly resolved. Different initial conditions could alter the relative weighting factors on the various exponential terms, but did not affect any of the individual time constants. The activation of the sodium conductance cannot be attributed to any number of independent and identical two-state subunits with first order transitions. The results of this and the previous paper are discussed in terms of the minimum kinetic scheme consistent with the data. Evidence is also presented suggesting that there may exist a small subpopuladon of channels with different kinetics and a faster rate of recovery from TTX block than the rest of the population.