Substance P decreases membrane conductance in neurons of the guinea pig hypothalamus in vitro.

Substance P (SP) depolarized the membrane and increased the spontaneous firing rate of neurons in slices of the guinea pig hypothalamus. These excitatory actions of SP were accompanied by a decrease in membrane conductance, and this reduction was observed even during a perfusion of the medium which was Ca2+ free and in which the concentration of Mg/+ had been increased to 12 mM. Therefore, the contribution of possible presynaptic or indirect effects of SP to the decreased membrane conductance can be ruled out. These observations suggest that SP exerts an excitatory action on neurons in the guinea pig hypothalamus by decreasing the membrane ionic permeability of these neurons.