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. In the trigeminal subnucleus caudalis (medullary dorsal horn) and in the spinal dorsal horn (the relaying centres for processing pain and sensory information), glycine inhibits the glutamate-evoked depolarization and depresses firing of neurons. The binding of glycine to its receptor produces a large increase in Cl- conductance, which causes membrane hyperpolarization. The selectivity and gating properties of glycine receptor channels have been well characterized; the glycine receptor molecules have also been purified. The amino-acid sequence, deduced from complementary DNA clones encoding one of the peptides (the 48K subunit), shows significant homology with gamma-aminobutyric acid A (GABAA) and nicotinic acetylcholine receptor subunits, suggesting that glycine receptors may belong to a superfamily of chemically gated channel proteins. 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. GS protein, which is sensitive to cholera toxin, was involved in the modulation.
Song
Y M
YM
Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77550.
Huang
L Y
LY
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D018118:Chloride Channels; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology; D005998:Glycine / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D008565:Membrane Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D014279:Trigeminal Nucleus, Spinal / Q000166:cytology / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018118:Chloride Channels; D008565:Membrane Proteins; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D005680:gamma-Aminobutyric Acid; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D007608:Kainic Acid; D005998:Glycine