Transmitter-mediated inhibition of N-type calcium channels in sensory neurons involves multiple GTP-binding proteins and subunits.
The modulation of voltage-activated Ca2+ channels by neurotransmitters and peptides is very likely a primary means of regulating Ca(2+)-dependent physiological functions such as neurosecretion, muscle contraction, and membrane excitability. In neurons, N-type Ca2+ channels (defined as omega-conotoxin GVIA-sensitive) are one prominent target for transmitter-mediated inhibition. This inhibition is widely thought to result from a shift in the voltage independence of channel gating. Recently, however, voltage-independent inhibition has also been described for N channels. As embryonic chick dorsal root ganglion neurons express both of these biophysically distinct modulatory pathways, we have utilized these cells to test the hypothesis that the voltage-dependent and -independent actions of transmitters are mediated by separate biochemical pathways. We have confirmed this hypothesis by demonstrating that the two modulatory mechanisms activated by a single transmitter involve not only different classes of G protein but also different G protein subunits.
Diversé-Pierluissi
M
M
Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Goldsmith
P K
PK
Dunlap
K
K
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D002642:Chick Embryo; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology* / Q000196:embryology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007700:Kinetics; D046911:Macromolecular Substances; D009475:Neurons, Afferent / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D046911:Macromolecular Substances; D018377:Neurotransmitter Agents; D010455:Peptides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D005680:gamma-Aminobutyric Acid; D020866:omega-Conotoxin GVIA; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D009638:Norepinephrine