Hexamethonium increases the excitability of sympathetic neurons by the blockade of the Ca2+-activated K+ channels.

Effects of hexamethonium (C6) on the excitability of sympathetic ganglion cells were examined by means of intracellular recording. When DC currents were injected, high concentrations of C6 significantly augmented the repetitive firing of the cells without any change in threshold voltage for initiation of the spike. The Ca2+-sensitive component of the after-hyperpolarization following a spike was reduced by C6 in a dose-dependent fashion (0.3 to 10 mM). C6 slightly affected parameters for the spike but neither the resting membrane potential nor the input membrane resistance. The amplitude of the Ca2+ spike (in the presence of 1 microM tetrodotoxin and 10 mM tetraethylammonium) was not affected even by 30 mM C6. Bee venom (0.3 micrograms/ml) which contains apamin showed similar effects. These results suggest that C6 blocks the Ca2+-activated K+ channels, resulting in an increase in excitability of the cells.