Comparison of 4-aminopyridine and tetrahydroaminoacridine on basal forebrain neurons

This study was designed to investigate the ability of 4-aminopyridine (4-AP) and tetrahydroaminoacridine (THA) to reduce several potassium conductances in cells of the medial septum and nucleus of the diagonal band. Intracellular recording and single electrode voltage-clamp techniques were used in an in vitro brain slice preparation. Both 4-AP (100-300 microM) and THA (300 microM) reduced a transient outward current (A-current), whereas only 4-AP increased the release of spontaneous postsynaptic potentials and significantly prolonged action potential duration. High concentrations of THA (1 mM) were needed to significantly increase action potential duration but these levels of THA were still ineffective in eliciting spontaneous postsynaptic potentials. THA (300 microM), but not 4-AP, had the additional effect of reducing time-dependent membrane rectification (Q-current) in one cell type. Our results demonstrate that both cholinergic and non-cholinergic cells are sensitive to pharmacological concentrations of both compounds.