Histamine promotes excitability in bovine adrenal chromaffin cells by inhibiting an M-current

The current study has investigated the electrophysiological responses evoked by histamine in bovine adrenal chromaffin cells using perforated-patch techniques. Histamine caused a transient hyperpolarization followed by a sustained depolarization of 7.2 +/- 1.4 mV associated with an increase in spontaneous action potential frequency. The hyperpolarization was abolished after depleting intracellular Ca2+ stores with thapsigargin (100 nM), and was reduced by 40% with apamin (100 nM). Membrane resistance increased by about 60 % during the histamine-induced depolarization suggesting inhibition of a K+ channel. An inward current relaxation, typical of an M-current, was observed in response to negative voltage steps from a holding potential of -30 mV. This current reversed at -81.6 +/- 1.8 mV and was abolished by the M-channel inhibitor linopirdine (100 muM). During application of histamine, the amplitude of M-currents recorded at a time corresponding with the sustained depolarization was reduced by 40%. No inward current rectification was observed in the range -150 to -70 mV, and glibenclamide (10 muM) had no effect on either resting membrane potential or the response to histamine. The results show that an M-current is present in bovine chromaffin cells and that this current is inhibited during sustained application of histamine, resulting in membrane depolarization and increased discharge of action potentials. These results demonstrate for the first time a possible mechanism coupling histamine receptors to activation of voltage-operated Ca2+ channels in these cells.