FACILITATION OF N-TYPE CALCIUM CURRENT IS DEPENDENT ON THE FREQUENCY OF ACTION POTENTIAL-LIKE DEPOLARIZATIONS IN DISSOCIATED CHOLINERGIC BASAL FOREBRAIN NEURONS OF THE GUINEA-PIG

Voltage-dependent inhibition of high voltage-activated (HVA) calcium c urrents by G-proteins can be transiently relieved (facilitated) by str ong depolarizing prepulses. However, with respect to the physiological significance of facilitation, it remains to be established if it can be induced by action potentials (AP) in central neurons. With the use of whole-cell recordings of dissociated cholinergic basal forebrain ne urons of the guinea pig, it is shown that the GTP gamma S-inhibited HV A currents that occur through N-ethylmaleimide (NEM)-sensitive G(i)-G( o) subtypes of G-proteins can be facilitated. Furthermore, although di fferent types of HVA channels are present in these neurons, facilitati on occurred mostly through disinhibition of the N-type current. On the basis of data indicating that the recovery from facilitation was rela tively slow, we tested if more physiological stimuli that crudely mimi cked APs (2 msec long depolarizations to 40 mV from a holding of simil ar to 50 mV) potentially could induce facilitation of HVA currents inh ibited by GTP gamma S and cholinergic agonists. Indeed, evidence is pr ovided that the extent of facilitation is dependent on both the number and frequency of AP-like depolarizations. These results suggest that firing rates and patterns of discharge of neurons could influence thei r responsiveness to transmitters acting on N-type HVA calcium channels .