The ionic basis of norepinephrine (NE) action was studied with intracellular recording techniques in the rat hippocampal slice. Topical application of NE caused, in CA1 neurons, a 3-4 mV hyperpolarization associated with a 10-20% decrease in input resistance. This effect was accompanied by a decrease in spontaneous action potential discharges and, in some cells, by a reduction in EPSPs produced by stimulation of the excitatory Schaffer collateral-commissural pathway. An analysis of the voltage and concentration dependency revealed that NE may activate two different mechanisms. Experiments performed to test this hypothesis have demonstrated that a short duration hyperpolarizing action of NE was still present in a low Cl- medium. The hyperpolarizing responses to NE were absent in ouabain-treated slices and in low temperature. Cyclic AMP produced a 3-4 mV hyperpolarization associated with minimal changes in input resistance. This effect of cAMP was blocked by ouabain. IBMX potentiated responses to low concentrations of NE. It is proposed that NE activates two mechanisms; one involves activation of Cl- conductance and the other activation of a Na+-K+ pump. This latter effect might be mediated by cAMP.
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