Group I mGluR activation turns on a voltage-gated inward current in hippocampal pyramidal cells

A unique property of the group I metabotropic glutamate receptor (mGluR)-induced depolarization in hippocampal cells is that the amplitude of the depolarization is larger when the response is elicited at more depolarized membrane potentials. Our understanding of the conductance mechanism underlying this voltage-dependent response is incomplete. Through the use of current-clamp and single-electrode voltage-clamp recordings in guinea pig hippocampal slices, we examined the group I mGluR-induced depolarization in CA3 pyramidal cells. The group I mGluR agonists (S)-3-hydroxyphenylglycine and (S)-3,5-dihydroxyphenylglycine turned on a voltage-gated inward current (I(mGluR(V))), which was pharmacologically distinct from the voltage-gated sodium and calcium currents intrinsic to the cells. I(mGluR(V)) was a slowly activating, noninactivating current with a threshold at about -75 mV. In addition to the activation of I(mGluR(V)), group I mGluR stimulation also produced a voltage-independent decrease in the K(+) conductance. Our results suggest that the depolarization induced by group I mGluR activation is generated by two ionic mechanisms-a heretofore unrecognized voltage-gated inward current (I(mGluR(V))) that is turned on by depolarization and a voltage-insensitive inward current that results from a turn-off of the K(+) conductance. The low-threshold and noninactivating properties of I(mGluR(V)) allow the current to play a significant role in setting the resting potential and firing pattern of CA3 pyramidal cells.