ACTION OF A METABOTROPIC GLUTAMATE-RECEPTOR AGONIST IN RAT LATERAL SEPTUM - INDUCTION OF A SODIUM-DEPENDENT INWARD AFTERCURRENT

The mechanism by which (1S,SR)-ACPD, a metabotropic glutamate receptor agonist, induces burst firing in lateral septal neurons of the rat wa s investigated in coronal brainstem slices. Membrane currents were cha racterized in voltage clamp using whole-cell recordings. In the presen ce of (1S,3R)-ACPD, following depolarizing voltage jumps, repolarizati on towards the holding potential generated an inward aftercurrent. It could have a plateau-like phase and decayed exponentially. This (1S,3R )-ACPD-dependent inward aftercurrent was accompanied by an increase in cell conductance and was reduced following partial replacement of ext racellular sodium by N-methyl-D-glucamine. It was unaffected by TEA or barium, and persisted in Cs-loaded neurons or following partial repla cement of extracellular chloride by isethionate. This suggests that it was mainly carried by sodium. Loading neurons with the calcium chelat or, BAPTA, or blocking transmembrane calcium currents, suppressed the (1S,3R)-ACPD-dependent aftercurrent. By contrast, partial replacement of extracellular sodium by Lithium did not affect it. Thus, this curre nt was dependent upon calcium influx but was not due to a sodium/calci um exchanger. It was probably mediated by G protein activation. Indeed , in neurons loaded with GTP-gamma-S, following depolarizing voltage j umps, repolarization towards the holding potential revealed an inward aftercurrent having properties similar to those of the (1S,SR)-ACPD-de pendent current. We suggest that (1S,3R)-ACPD induced calcium-activate d non-selective channels. In the presence of this agonist, a depolariz ation-evoked calcium influx could thus evoke a cationic inward current . This current probably promotes the burst firing observed in lateral septal neurons in current clamp. (C) 1997 Elsevier Science B.V.