Voltage-clamp analysis of muscarinic excitation in hippocampal neurons

Pyramidal cells in the CA1 field of guinea pig hippocampal slices were voltage-clamped using a single microelectrode, at 23-30 degrees C. Small inwardly relaxing currents triggered by step hyperpolarizations from holding potentials of -80 to -40 mV were investigated. Inward relaxations occurring for negative steps between -40 mV and -70 mV resembled M-currents of sympathetic ganglion cells: they were abolished by addition of carbachol, muscarine or bethanechol, as well as by 1 mM barium; the relaxations appeared to invert at around -80 mV; they became faster at more negative potentials; and the inversion potential was shifted positively by raising external K+ concentration. Inward relaxations triggered by steps negative to -80 mV, in contrast, appeared to reflect passage of another current species, which has been labelled IQ. Thus IQ did not invert negative to -80 mV, it was insensitive to muscarinic agonists or to barium, and it was blocked by 0.5-3 mM cesium (which does not block IM). Turn-on of IQ causes the well known droop in the hyperpolarizing electrotonic potential in these cells. The combined effects of IQ and IM make the steady-state current-voltage relation of CA1 cells slightly sigmoidal around rest potential. It is suggested that activation of cholinergic septal inputs to the hippocampus facilitates repetitive firing of pyramidal cells by turning off the M-conductance, without much change in the resting potential of the cell.