Effects of quinidine and quinine on the excitability of pyramidal neurons in guinea-pig hippocampal slices

Effects of quinidine (25M–1mM) and its stereoisomer, quinine (1–5 mM), on the excitability of CA3 pyramidal neurons were investigated in guinea-pig hippocampal slices using intracellular recording techniques. At concentrations of quinidine higher than 100 M (and higher than 1 mM for quinine), 1) the resting potential shifted to the depolarizing direction with an increase of the input resistance, 2) the spike duration was prolonged, 3) the spike amplitude was decreased, 4) the late component of the afterhyperpolarization (AHP) (caused by the activity of the Ca²⁺-mediated K conductance) were suppressed, and 5) finally, neurons became inexcitable. The results indicate that the blocking action of quinidine and quinine is not specific to the Ca²⁺-mediated K conductance in mammalian hippocampal neurons, and that this conductance is much less sensitive to the drugs in comparison with other preparations.