Certain antiepileptic drugs are known to block sodium and calcium channels of excitable membranes. These channels are responsible for generation of action potentials. Various natural toxins, chemicals, and therapeutic drugs have been found to modify the gating kinetics of the sodium and/or calcium channels, thereby altering the excitation. Studies of such chemical modulations of the sodium and calcium channel gating provide the basis for understanding the mechanisms underlying epilepsies and the actions of antiepileptic drugs. Tetrodotoxin blocks the sodium channels, whereas batrachotoxin (BTX), grayanotoxin (GTX), and pyrethroids modify a population of the sodium channels to give rise to an extremely slow opening and/or closing. Patch-clamp techniques developed during the past few years permit measurements of opening and closing of individual ionic channels. When a membrane patch isolated from a neuroblastoma cell is depolarized, square inward currents of about 1 pA in amplitude and 2 msec in duration are observed at 10 degrees C. After exposure of the membrane to BTX, the open time is prolonged, the single-current amplitude is reduced, and channel opening is observed at large negative potentials at which no opening is expected to occur in normal preparations. In the BTX-poisoned membrane, there are two separate groups of the sodium channels, one exhibiting the normal characteristics and the other exhibiting a prolonged opening and reduced amplitude. Tetramethrin also modifies the single sodium channel in a similar manner to BTX, but fails to affect the amplitude of single-channel current. Neuroblastoma cells are also endowed with calcium channels, which undergo inactivation in a manner dependent upon membrane potential.