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Volume 17, Number 19, Issue of October 1, 1997 pp. 7307-7315
Copyright ©1997 Society for Neuroscience

Distinct Contributions of High- and Low-Voltage-Activated Calcium Currents to Afterhyperpolarizations in Cholinergic Nucleus Basalis Neurons of the Guinea Pig

Received Jan. 21, 1997; revised July 18, 1997; accepted July 22, 1997.

Sylvain Williams, Mauro Serafin, Michel Mühlethaler, and Laurent Bernheim

Département de Physiologie, Centre Médical Universitaire, 1211 Genève 4, Switzerland

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. Neurons with somata >25 µM were studied because 80% of them stained positively for choline acetyltransferase and had electrophysiological characteristics identical to those of cholinergic NB neurons previously recorded in basal forebrain slices. Calcium currents of cholinergic NB neurons first were dissected pharmacologically into an amiloride-sensitive LVA and at least five subtypes of HVA currents. Approximately 17% of the total HVA current was sensitive to nifedipine (3 µM), 35% to -conotoxin-GVIA (200-400 nM), 10% to -Agatoxin-IVA (100 nM), and 20% to -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 µM). We then assessed pharmacologically the role that LVA and HVA currents had in activating the apamin-insensitive AHP elicited by a long train of action potentials (sAHP) and the AHP evoked either by a short burst of action potentials or by a single action potential (mAHP) that is known to be apamin-sensitive. During sAHPs, ~60% of the hyperpolarization was activated by calcium flowing through N-type channels and ~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 (~60 and 30%, respectively), whereas L-, P-, and Q-type channels were not implicated significantly. It is concluded that in cholinergic NB neurons various subtypes of calcium channels can differentially activate the apamin-sensitive mAHP and the apamin-insensitive sAHP.

Key words: acetylcholine; afterhyperpolarization; arousal; basal forebrain; calcium currents; low-threshold spike

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