Modulation of glycine receptor chloride channels by cAMP-dependent protein kinase in spinal trigeminal neurons

GLYCINE is an important inhibitory transmitter in the brainstem and spinal cord^1,2. In the trigeminal subnucleus caudalis (medullary dorsal horn) and in the spinal dorsal horn (the relaying centres for processing pain and sensory information^3-5), glycine inhibits the glutamate-evoked depolarization and depresses firing of neurons⁶. The binding of glycine to its receptor produces a large increase in Cl^- conductance, which causes membrane hyper-polarization⁷. The selectivity and gating properties of glycine receptor channels have been well characterized⁸; the glycine receptor molecules have also been purified^9-11. The amino-acid sequence, deduced from complementary DNA clones encoding one of the peptides (the 48K subunit)¹², shows significant homology with γ-aminobutyric acid A (GABA_A) and nicotinic acetylcholine receptor subunits, suggesting that glycine receptors may belong to a superfamily of chemically gated channel proteins^12,13. However, very little is known about the modulation of glycine receptor channels. We have investigated the regulation of strychnine-sensitive glycine receptor channels by cyclic AMP-dependent protein kinase in neurons isolated from spinal trigeminal nucleus of rat and report here that the protein kinase A dramatically increased the glycine-induced Cl^- currents by increasing the probability of the channel openings. G_S protein, which is sensitive to cholera toxin, was involved in the modulation.