Voltage-dependent inhibition and facilitation of Ca channel activation by GTP-gamma-S and Ca-agonists in adult rat sensory neurons.

Intracellular application of guanosine 5'-O-3-thiotriphosphate (GTP-gamma-S, 100 microM) causes a slow down of high-threshold Ca channel activation in adult rat sensory neurons that is relieved by strong depolarizations or by the Ca agonist Bay K 8644 (5 microM). Recovery from GTP-gamma-S inhibition is usually accompanied by an increase in Ca current amplitude (facilitation) and is insensitive to holding potential (-60 to -90 mV). Inhibition and facilitation of Ca currents are also little affected by nifedipine (5 microM) or by cell incubation with omega-conotoxin (omega-CgTx, 3.2 microM). We conclude that both slowdown of Ca channel activation by GTP-gamma-S and facilitation by strong depolarizations or by Ca agonists derive from a common process in which G-protein activation, membrane voltage and Ca agonist receptors interact to modulate neuronal Ca channel gatings.