Norepinephrine (NE) and gamma-aminobutyric acid (GABA) inhibit N-type
calcium channels in embryonic chick sensory neurons. We demonstrate he
re that the modulatory actions of the two transmitters are mediated th
rough distinct biochemical pathways. Intracellular application of the
pseudosubstrate inhibitor for protein kinase C blocks the inhibition p
roduced by NE (and the protein kinase C activator oleoylacetylglycerol
), but not that produced by GABA. Calcium current inhibition produced
by oleoylacetylglycerol occludes inhibition by subsequent application
of NE; GABA-mediated inhibition, however, is not eliminated by prior a
ctivation of protein kinase C. These results demonstrate that multiple
biochemical pathways converge to control N-type calcium channel funct
ion.