DISTINCT CONTRIBUTIONS OF HIGH-VOLTAGE-ACTIVATED AND LOW-VOLTAGE-ACTIVATED CALCIUM CURRENTS TO AFTERHYPERPOLARIZATIONS IN CHOLINERGIC NUCLEUS BASALIS NEURONS OF THE GUINEA-PIG

The contributions made by low- (LVA) and high-voltage-activated (HVA) calcium currents to afterhyperpolarizations (AHPs) of nucleus basalis (NB) cholinergic neurons were investigated in dissociated cells, Neuro ns with somata >25 mu M were studied because 80% of them stained posit ively for choline acetyltransferase and had electrophysiological chara cteristics identical to those of cholinergic NB neurons previously rec orded in basal forebrain slices, Calcium currents of cholinergic NB ne urons first were dissected pharmacologically into an amiloride-sensiti ve LVA and at least five subtypes of HVA currents, Approximately 17% o f the total HVA current was sensitive to nifedipine (3 mu M), 35% to o mega-conotoxin-GVIA (200-400 nM), 10% to omega-Agatoxin-IVA (100 nM), and 20% to omega-Agatoxin-IVA (300-500 nM), suggesting the presence of L-, N-, P-, and Q-type channels, respectively, A remaining current (R -type) resistant to these antagonists was blocked by cadmium (100-200 mu M). We then assessed pharmacologically the role that LVA and HVA cu rrents had in activating the apamin-insensitive AHP elicited by a long train of action potentials (sAHP) and the AHP evoked either by a shor t burst of action potentials or by a single action potential (mAHP) th at is known to be apamin-sensitive, During sAHPs, similar to 60% of th e hyperpolarization was activated by calcium flowing through N-type ch annels and similar to 20% through P-type channels, whereas T-, L-, and Q-type channels were not involved significantly, In contrast, during mAHPs, N- and T-type channels played key roles (similar to 60 and 30%, respectively), whereas L-, P-, and Q-type channels were not implicate d significantly. It is concluded that in cholinergic NB neurons variou s subtypes of calcium channels can differentially activate the apamin- sensitive mAHP and the apamin-insensitive sAHP.