The effect of phenytoin on the action potential of a vertebrate spinal neuron

The effect of phenytoin (PTN) 20 microgram/ml was tested on the passive membrane properties and the action potential of the dorsal cells in the spinal cord of the river lamprey. Dorsal cells are primary sensory neurons with no synaptic input, and thus allow examination of membrane properties in the absence of contaminating synaptic currents. PTN did not affect the resting membrane potential and slightly raised the input resistance. However, it greatly raised the threshold voltage and current for activation of action potentials by intracellularly injected current. It also reduced the maximum rate of rise of the action potential, the spike overshoot and the spike undershoot, while increasing the spike duration. In contrast to findings in other vertebrate sensory neurons, dorsal cell action potentials were blocked in zero sodium or tetrodotoxin, and not affected by zero calcium or 1 mM manganese. Thus they PTN on dorsal cells is that it partially blocks the activated sodium conductance increase of the action potential. Because a long delay was observed for maximal effect of PTN and for washout, it is postulated that the drug may require partitioning into the lipid membrane, or entry into the cell for its pharmacological action.