The agonist effect of Bay K 8644 on neuronal calcium channel currents is promoted by G-protein activation.

Voltage-activated Ca2+ channel currents were recorded from cultured rat dorsal root ganglion neurones using the whole cell clamp technique. Inclusion of 500 microM guanosine 5'-O(3-thio)triphosphate (GTP-gamma-S) in the patch pipette solution resulted in inhibition of the transient component of the Ca2+ channel current. The slowly activating, relatively non-activating Ca2+ channel current which remained in the presence of intracellular GTP-gamma-S was potentiated by the 1,4-dihydropyridine Ca2+ channel agonist Bay K 8644 (5 microM). The percentage increase induced by Bay K 8644 was greater in cells with internal GTP-gamma-S than in control cells. Pretreating cells with pertussis toxin resulted in Bay K 8644 inhibiting rather than increasing Ca2+ channel currents. These results support the hypothesis that L-type Ca2+ channel activity underlies the sustained Ca2+ channel currents which are not inhibited by GTP-gamma-S and that Ca2+ channel ligands require activation of a pertussis toxin-sensitive G protein to exert their agonist effects.