Transmitter-mediated inhibition of N-type calcium channels in sensory neurons involves multiple GTP-binding proteins and subunits

• Published in: Neuron (Cambridge, Mass.) Mass.), 1995, Vol.14 (1), p.191-200
• Main Authors: Diverse-Pierluissi, Maria, Goldsmith, Paul K, Dunlap, Kathleen
• Format: Article
• Language: English
• Subjects: Animals; Calcium Channel Blockers - pharmacology; Calcium Channels - physiology; Chick Embryo; Electric Conductivity; gamma-Aminobutyric Acid - pharmacology; Ganglia, Spinal - cytology; Ganglia, Spinal - embryology; GTP-Binding Proteins - physiology; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Kinetics; Macromolecular Substances; Neurons, Afferent - physiology; Neurotransmitter Agents - pharmacology; Norepinephrine - pharmacology; omega-Conotoxin GVIA; Peptides - pharmacology; Protein Kinase C - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/0896-6273(95)90254-6

The modulation of voltage-activated Cat+ 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 Ca 2+ channels (defined as ω-conotoxin GVIA-sensitive) are one prominent target for transmitter-mediated inhibition. This inhibition is widely thought to result from a shift in the voltage dependence 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.