Pre- and postsynaptic effect of galanin on excitatory synaptic transmission in rat spinal dorsal horn neurons

Abstract

Galanin, a 29 ⁄ 30 amino acid neuropeptide, and three types (GalR1-3) of receptors for this neuropeptide, which are expressed in rat dorsal root ganglion neurons and spinal dorsal horn neurons, play a pivotal role in regulating nociceptive transmission to the spinal dorsal horn from the periphery. Intrathecal administration of galanin in rats modulates nociceptive behavior in a biphasic manner such that galanin at low and high doses produces nociception and antinociception, respectively. In order to know cellular mechanisms for this effect, we investigated the effect of galanin on glutamatergic spontaneous excitatory synaptic transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by use of the whole cell patch-clamp technique. In 83% of the neurons examined (n=29), galanin (0.03 µM) superfused for 2 min increased the frequency of spontaneous excitatory postsynaptic current (sEPSC) recorded at -70 mV without a change in its amplitude and also in holding currents. The remaining neurons produced a small outward (n=4) or inward current (n=1). This presynaptic effect was dose-dependent with an EC50 value of 0.0029 µM, and was mimicked by a selective GalR2⁄R3 agonist galanin (2-11) but not a selective GalR1 agonist M617. Superfusing galanin at a higher dose such as 0.1 µM for 2 min produced an outward current in 39% of SG neurons tested (n=33). Twelve % of the SG neurons had an inward current and the remaining neurons did not change holding currents. The outward current produced by galanin had an EC50 value of 0.042 µM, and was mimicked by M617 but not galanin (2-11). The sEPSC frequency increase and outward current persisted in the presence of a Na+-channel blocker tetrodotoxin.It is concluded that galanin at lower doses enhances the spontaneous release of L-glutamate from nerve terminals by activating GalR2⁄R3 while galanin at higher doses produces a membrane hyperpolarization by activating GalR1 in the SG. This pre- and postsynaptic effects could contribute to at least a part of the behavioral effect of galanin.