The mechanism of spontaneous firing in histamine neurons.

Histaminergic neurons project to virtually the whole central nervous system and display regular firing related to behavioral state. Electrophysiological studies of histaminergic neurons show that these neurons fire in a beating pacemaker pattern, which is intrinsic to individual neurons. Onset of an action potential occurs as the result of a slow depolarizing potential, which consists of voltage dependent calcium current(s) and non-inactivating sodium current. The calcium component is a voltage-dependent current activated by the return to threshold following the afterhyperpolarization (AHP) while the sodium current appears to be persistent. The action potential is followed by an AHP, which limits firing rate. The AHP is due to two potassium currents, one voltage-, the other calcium-dependent; it determines the amount of voltage-dependent currents available for activation. We show original results indicating that calcium current can be activated during AHP-like ramps and that the amount of calcium current near threshold is strongly dependent on the membrane potential and on the size of the AHP. The amount of calcium entering during the action potential will determine the duration of the AHP and thus, the firing rate.