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 Ca2+-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 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.