Activation of phosphoinositide turnover and protein kinase C by neurotransmitters that modulate calcium channels in embryonic chick sensory neurons.
Gamma aminobutyric acid (GABA) and norepinephrine modulate the excitability of primary chick sensory neurons by decreasing the voltage dependent Ca current. Although previous electrophysiological studies indicate that neurotransmitter modulation of the Ca current in these neurons involves protein kinase C, the biochemical aspects of this mechanism have not been examined directly. We find that both norepinephrine (via a unique alpha receptor subtype) and GABA (via GABAb receptors) linked to pertussis toxin sensitive pathways, stimulate the metabolism of membrane phosphatidylinositol phospholipids in primary chick sensory neurons. In addition, norepinephrine causes the rapid translocation of C kinase activity from cytosolic to membrane associated distribution, consistent with its rapid activation in response to applied neurotransmitter. The pharmacology, pertussis toxin sensitivity and time course of the biochemical changes due to neurotransmitter treatment parallel the effects of these transmitters on calcium current modulation. These biochemical studies confirm the hypothesis that activation of protein kinase C is critically involved in calcium channel modulation in embryonic chick sensory neurons.
Harish
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Department of Anatomy and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
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D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002642:Chick Embryo; D019204:GTP-Binding Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; D005680:gamma-Aminobutyric Acid; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D001418:Baclofen; D009638:Norepinephrine