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. Electrophysiologic al studies of histaminergic neurons show that these neurons fire in a beati ng pacemaker pattern, which is intrinsic to individual neurons. Onset of an action potential occurs as the result of a slow depolarizing potential, wh ich consists of voltage dependent calcium current(s) and non-inactivating s odium current. The calcium component is a voltage-dependent current activat ed by the return to threshold following the afterhyperpolarization (AHP) wh ile the sodium current appears to be persistent. The action potential is fo llowed by an AHP, which limits firing rate. The AHP is due to two potassium currents, one voltage-, the other calcium-dependent; it determines the amo unt of voltage-dependent currents available for activation. We show origina l results indicating that calcium current can be activated during AHP-like ramps and that the amount of calcium current near threshold is strongly dep endent 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. (C) 2001 Elsevier Science B.V. All righ ts reserved.