Specific inhibitors of protein kinase C block transmitter-induced modulation of sensory neuron calcium current.
Modulation of neuronal, voltage-dependent calcium current has been described for a number of transmitters and peptides, but the biochemical basis for this phenomenon has not been completely identified. In several cases protein kinase C (PKC) is thought to mediate transmitter inhibition of calcium current; however, a lack of specific PKC inhibitors has hampered a direct physiological test of this idea. We have used the whole-cell, tight-seal configuration of the patch-clamp technique to apply intracellularly two specific PKC inhibitors to the cell bodies of embryonic chick sensory neurons. Both inhibitors, a 17 kd protein purified from bovine brain and a synthetic 13 amino acid "pseudosubstrate" peptide, blocked inhibition of calcium current by either norepinephrine or an exogenously applied PKC activator. These results provide strong evidence that activation of PKC is a prerequisite for the modulation of sensory neuron calcium current by norepinephrine.
Rane
S G
SG
Department of Physiology, Tufts University Medical School, Boston, Massachusetts 02111.
Walsh
M P
MP
McDonald
J R
JR
Dunlap
K
K
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D004075:Diglycerides; D018377:Neurotransmitter Agents; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D002118:Calcium; D009638:Norepinephrine