ACTIVATION OF A NONSELECTIVE CATIONIC CONDUCTANCE BY METABOTROPIC GLUTAMATERGIC AND MUSCARINIC AGONISTS IN CA3 PYRAMIDAL NEURONS OF THE RATHIPPOCAMPUS

We have characterized a cationic membrane conductance activated by met abotropic glutamatergic and muscarinic cholinergic agonists in CA3 neu rons in hippocampal slice cultures using the patch-clamp technique, Wh en the potassium concentration in the superfusing fluid was raised abo ve 5 mM, a biphasic current was observed in cells held at -60 mV in re sponse to stimulation of postsynaptic metabotropic glutamate receptors (mGluRs) with 1S,3R-ACPD (50 mu M) or muscarinic receptors with metha choline (MCh, 5 mu M). The initial inward component was due to an incr ease in a cationic membrane conductance as determined by its reversal potential and its sensitivity to changes in extracellular K+ or Na+, T he conductance underlying this current displayed no apparent voltage s ensitivity over the range -120 to -50 mV, The response was reduced by extracellular application of Ba2+, Cd2+, Mg2+, or TEA, whereas extrace llular Cs' or loading cells with BAPTA or Cs' did not affect the curre nt, The effects of 1S,3R-ACPD were reversibly inhibited by bath-applie d MCPG, an antagonist at mGluRs, Experiments with atropine and pirenze pine indicated that non-M, muscarinic receptors mediated the MCh-induc ed current, A decrease in a resting leak potassium conductance (I-K,I- leak) was responsible for the late component of the 1S,3R-ACPD- and MC h-induced response, seen as an outward current in the bathing solution with high K+ concentration, Loading cells with GDP beta S, GTP gamma S, or GTP did not alter the cationic current, while, in the same cells , the reduction in I-K,I-leak was abolished or irreversibly activated, Single-channel recordings of cationic channel activity in the cell-at tached configuration provided evidence for the requirement of second m essengers in coupling these receptors to the cationic channels. The da ta indicate that in addition to the previously described reduction of I-K,I-leak, I-M, and I-AHP, both 1S,3R-ACPD and MCh activate a nonsele ctive cationic conductance that is clearly revealed upon elevating ext ernal K+ concentration, This current is mediated by activation of meta botropic receptors, although no evidence could be obtained to show an involvement of G-proteins.