The electrical excitability of 3 lines of rat pheochromocytoma (PC12) cells were determined under current-clamp recording conditions. In the presence of nerve growth factor (NGF), PC12(A) 'control' cells expressed high levels of GAP-43 protein, PC12(B) cells were highly deficient in GAP-43, and PC12(AB) cells, created by transfection of PC12(B) cells with a rat GAP-43 gene construct, expressed high levels of GAP-43. All 3 lines had similar resting membrane potentials, but significantly greater proportions of GAP-43-containing PC12(A) and PC12(AB) cells exhibited spiking in response to depolarizing current pulses. These spikes were resistant to TTX, were greatly enhanced in TEA and TTX, and were substantially reduced by L-type Ca(2+)-channel antagonists. GAP-43 expression may regulate PC12 cell excitability following NGF treatment, as reflected in a lower proportion of cells capable of discharging with Ca(2+)-spikes in a GAP-43-deficient cell line.