Actions of substance P on rat spinal dorsal horn neurones.

The membrane actions of substance P (SP) and the effects on the Ca-dependent action potential of dorsal horn neurones have been investigated by means of intracellular recording techniques in the immature rat in vitro spinal cord slice preparation. Bath application of SP (2 X 10(-6) to 1 X 10(-5) M) induced a biphasic membrane response consisting of an initial hyperpolarization followed by a depolarization in about one-third of the cells examined. Initial hyperpolarization was not observed when synaptic activity was blocked by perfusing the slice with a tetrodotoxin-containing or low Ca, high Mg Ringer solution. This result is consistent with a presynaptic action of SP mediated through excitation of inhibitory interneurones. This interpretation was supported by recording of repetitive spontaneous inhibitory post-synaptic potential (i.p.s.p.)-like hyperpolarizing potentials during the initial hyperpolarization. When Co ions were used to block voltage-dependent Ca conductance and possible indirect presynaptic actions, SP induced only a small depolarization of membrane potential. It seems, therefore, that Ca conductance may have contributed to the depolarizing phase of the SP response, either through its mediation of synaptic transmission or through direct effects as a charge carrier for inward current. When tetrodotoxin was used, the SP-induced increase in neuronal input resistance was not modified, although depolarization was slightly diminished. In contrast, in medium containing tetrodotoxin and tetraethylammonium, the SP-depolarizing response was enhanced and accompanied by a small decrease in input resistance and firing of Ca spikes. These results suggest that SP-induced depolarization might be a consequence of a reduction in a voltage-dependent K conductance allowing Na and/or Ca conductances to dominate. SP modified the duration of Ca-dependent action potentials of dorsal horn neurones, the most consistent change being an initial dose-dependent and reversible decrease in the spike duration. The decrease in Ca spike duration was associated with a small reduction in the rate of rise and peak amplitude, and a significant parallel increase in dV/dt of the falling phase of the Ca spike. Our data indicate that the initial decrease in Ca spike duration was not due to the depolarizing action of SP, although shunting of the membrane resistance, either through presynaptic or post-synaptic mechanisms, has not been ruled out. Alternatively, these data are consistent with the possibility that SP shortens the duration of the Ca spike by decreasing a voltage-sensitive inward Ca current and/or augmenting an outward K current.(ABSTRACT TRUNCATED AT 400 WORDS)