Tachykinins modulate multiple ionic conductances in voltage-clamped rat spinal dorsal horn neurons

1. The membrane actions of substance P (SP) and a related tachykinin, neurokinin A (NKA), have been investigated by means of a single-electrode, voltage-clamp technique in the immature rat dorsal horn neurons using an in vitro spinal cord slice preparation. 2. When the membrane potential was held at the resting level of between -75 and -55 mV, bath application of SP or NKA (10(-7) to 10(-5) M, for 1-3 min) induced an inward shift in the holding current lasting several minutes. The magnitude of this effect varied between 10 and 400 pA depending on the concentration of the peptides and the holding potential. 3. When a dorsal horn neuron was held at the resting level and subjected to 1-s depolarizing commands to membrane potentials between -60 and -35 mV, slow inward relaxations and inward tail currents, the latter on repolarization to the holding potential, were recorded. During the tachykinin-induced inward shift in the holding current, the inward relaxation and the tail current were augmented in a dose-related manner. 4. The SP-induced augmentation of the slow inward relaxation and the inward tail current is likely to be due to the enhancement of the activation of the Ca2+ current, because the effect was present, and even augmented in a zero-Ca2+, Ba2+-containing solution, it was reduced or completely abolished by zero-Ca2+, Co2+-, or Mg2+-containing solutions and is largely independent of the changes in external Na+, K+, or Cl- ions. Moreover, in the presence of the K+-channel blocker, tetraethylammonium (TEA), the effect is increased. 5. Depolarizing voltage commands to potentials positive to -35 mV evoked a large, outward K+ current response in the dorsal horn neurons, which was in part Ca2+-sensitive. The outward current response was augmented by SP. The SP effect persists, although being reduced in a zero-Ca2+, Ba2+- or Co2+-containing solutions. 6. In a zero-Ca2+ solution containing Co2+ and TEA, the augmentation of the Ca2+ current and the outward K+ current by SP was abolished. However, the SP-induced increase in a Ca2+-sensitive, voltage-insensitive conductance remained, although being reduced, and the response showed a reversal at about -28 mV. This current may be a result of a tachykinin-activated nonspecific increase in cationic permeability of the membrane of dorsal horn neurons, because the current is reduced by more than one-half when Na+ or Ca2+ is removed from the bathing medium.(ABSTRACT TRUNCATED AT 400 WORDS)