Glutamate-induced action potentials are preceded by regenerative prepotentials in rat hippocampal pyramidal cells in vitro.

(1) The responses of CA1 pyramidal cells to short glutamate pulses (10-50 ms) delivered at sensitive spots in the apical dendrites have been analysed by intracellular recording. (2) The glutamate pulses elicited stable depolarizing responses in a dose- and frequency-dependent manner. (3) When a single action potential with a firing probability around 0.5 was elicited, a subtraction procedure showed that a slow depolarizing ramp preceded each spike. We call this ramp the glutamate-induced prepotential (GluPP). (4) In contrast to the upward convex subthreshold depolarization the GluPP was upward concave. (5) The GluPP amplitude and time course increased with depolarization of the membrane, a phenomenon which appears to be connected to the elevation of action potential threshold. (6) The GluPP was regenerative since once started, it ended in an action potential. (7) A specific N-methyl-D-aspartate receptor antagonist, DL-2-amino-5-phosphonovaleric acid (50 microM) reduced the glutamate-induced depolarization, but did not affect the form or amplitude of GluPP, once the latter was induced. (8) It is concluded that short glutamate pulses elicited action potentials through a prepotential mechanism, similar to the slow prepotentials induced by long depolarizing current pulses across the soma membrane. (9) A possible physiological role for the GluPP is discussed.