Reconstruction of action potential development from whole-cell currents of differentiating spinal neurons

The duration and ionic dependence of action potentials are developmentally regulated. Voltage-clamp recordings of amphibian spinal neurons have revealed alterations in five currents. To determine whether the changes in the currents are sufficient to produce the change in action potential duration and ionic dependence, we constructed a Hodgkin-Huxley model of electrical excitability of these neurons. The model shows that the equations describing the voltage-clamped currents of young and mature neurons generate action potentials appropriate in duration and ionic dependence for each developmental stage. Moreover, the observed changes in the currents are quantitatively sufficient to produce the changes in the action potential. The effect of the change in each current is detectable in the model. However, the increase in amplitude of the delayed-rectifier potassium current has the largest effect. The model further shows that changes in action potential duration could be achieved with changes in kinetics rather than amplitude of this current, or with changes in amplitudes of other currents. Thus, although increase in amplitude of the delayed rectifier plays a pivotal role in the maturation of excitability, it is not uniquely positioned to govern the action potential duration.