Interplay between activation of GIRK current and deactivation of Ih modifies temporal integration of excitatory input in CA1 pyramidal cells.

Trains of brief iontophoretic glutamate pulses were delivered onto the apical dendrites of CA1 pyramidal cells at variable frequencies (3-100 Hz) to examine how the activation of a G protein-activated, inwardly rectifying K(+) (GIRK) conductance alters the postsynaptic processing of repetitive excitatory input. Application of the GIRK channel agonist baclofen (20 microM) reduced the amplitude of individual glutamate-evoked postsynaptic potentials (GPSPs) and attenuated summation of GPSPs so that higher stimulus intensities were required to fire the cell. Notably, GIRK channel activation not only decreased GPSPs, but also suppressed the subsequent afterhyperpolarization (AHP), which arises from a transient deactivation of the hyperpolarization-activated cation current (I(h)). Voltage-clamp recordings ruled out a direct modulatory action of baclofen on I(h). GIRK channel activation alone accounts for AHP suppression, firstly because, with smaller GPSP amplitudes, fewer I(h) channels are deactivated, resulting in a diminished AHP, and secondly because, owing to its progressive increase in the hyperpolarizing direction, the GIRK conductance shunts a large portion of the remaining AHP. We provide experimental evidence that the suppression of the I(h)-dependent AHP by GIRK channel activation bears particular significance on the processing of repetitive excitatory inputs at frequencies at which the deactivation kinetics of I(h) exert a prominent depressing effect. In functional terms, activation of GIRK current not only produces a time-independent mitigation of incoming excitatory input, which results directly from the opening of an instantaneous K(+) conductance, but might also cause a time-dependent redistribution of synaptic weight within a stimulus train, which we link to an interplay with the deactivation of I(h).