Blockade of SK-type Ca2+-activated K+ channels uncovers a Ca2+-dependent slow afterdepolarization in nigral dopamine neurons

Sharp electrode current-clamp recording techniques were used to characteriz e the response of nigral dopamine (DA)containing neurons in rat brain slice s to injected current pulses applied in the presence of TTX (2 mu M) and un der conditions in which apamin-sensitive Ca2+-activated K+ channels were bl ocked. Addition of apamin (100-300 nM) to perfusion solutions containing TT X blocked the pacemaker oscillation in membrane voltage evoked by depolariz ing current pulses and revealed an afterdepolarization (ADP) that appeared as a shoulder on the falling phase of the voltage response. ADP were preced ed by a ramp-shaped slow depolarization and followed by an apamin-insensiti ve hyperpolarizing afterpotential (HAP). Although ADPs were observed in all apamin-treated cells, the duration of the response varied considerably bet ween individual neurons and was strongly potentiated by the addition of TEA (2-3 mM). In the presence of TTX, TEA, and apamin, optimal stimulus parame ters (0.1 nA, 200-ms duration at -55 to -68 mV) evoked ADP ranging from 80 to 1,020 ms in duration (355.3 +/- 56.5 ms, n = 16). Both the ramp-shaped s low depolarization and the ensuing ADP were markedly voltage dependent but appeared to be mediated by separate conductance mechanisms. Thus, although bath application of nifedipine (10-30 mu M) or low Ca2+, high Mg2+ Ringer b locked the ADP without affecting the ramp potential, equimolar substitution of Co2+ for Ca2+ blocked both components of the voltage response. Nominal Ca2+ Ringer containing Co2+ also blocked the HAP evoked between -55 and -68 mV. We conclude that the ADP elicited in DA neurons after blockade of apam in-sensitive Ca2+-activated K+ channels is mediated by a voltage-dependent, L-type Ca2+ channel and represents a transient form of the regenerative pl ateau oscillation in membrane potential previously shown to underlie apamin -induced bursting activity. These data provide further support for the noti on that modulation of apamin-sensitive Ca2+-activated K+ channels in DA neu rons exerts a permissive effect on the conductances that are involved in th e expression of phasic activity.