Neurotransmitter modulation of calcium channels in rat sympathetic neurons.
Adrenergic, cholinergic, and a variety of peptide neurotransmitters are known to modulate Ca currents in peripheral neurons. Using a protocol that allows for simultaneous assessment of effects on dihydropyridine (DHP)-sensitive and DHP-insensitive current components, we compared the actions of norepinephrine (NE), bethanechol (BeCh), and neuropeptide Y (NPY) on Ca currents in neonatal rat superior cervical ganglion neurons. Here, we show that these transmitters selectively depress the activity of DHP-insensitive Ca channels. Intracellular application of GTP-gamma-S, an activator of GTP-binding proteins, also exclusively affected the DHP-insensitive current, whereas 1,2-oleoylacetylglycerol (OAG), a protein kinase C (PKC) activator, depressed both the DHP-sensitive and DHP-insensitive currents. Pertussis toxin interrupted the coupling between NE and its effector, whereas three different inhibitors of PKC did not. Thus, we confirmed that the selective actions of the transmitters on Ca current appear to be mediated via GTP-binding proteins, but we found no evidence for direct involvement of PKC and conclude that the observed actions of OAG are distinct from those mediated by the neurotransmitters studied.
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts 02115.
M R
MR
Plummer
A
A
Rittenhouse
M
M
Kanevsky
P
P
Hess
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats
D001626:Bethanechol Compounds; D015220:Calcium Channels; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D018723:Bethanechol; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D009638:Norepinephrine