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α2-Adrenoceptors regulate the efficacy at the sympatho-effector junction by means of a feedback inhibition of transmitter release. In chick sympathetic neurons, the mechanism involves an inhibition of N-type calcium channels, and we now present evidence that this effect involves an atypical, phorbol ester-insensitive protein kinase C (PKC). The inhibition of voltage-gated Ca2+ currents by the specific α2-adrenergic agonist UK 14,304 was significantly attenuated when the PKC inhibitors PKCI(19–36), staurosporine, or calphostin C were included in the internal solution used to fill the patch pipettes, or if staurosporine or calphostin C were applied extracellularly; however, phorbol esters as classical activators of PKC or oleoylacetylglycerol did not mimic the effect of UK 14,304, and chronic exposure to 4-β-phorbol dibutyrate (PDBu) did not attenuate it, even though PKCα and -ε isozymes were translocated to plasma membranes by PDBu. The atypical isozyme PKCζ was translocated by 100 μm arachidonic acid (AA), but not by PDBu; 100 μm AA and linoleic acid inhibited voltage-activated Ca2+ currents, and this effect was attenuated when PKCI(19–36) was added to the patch pipette solution. Our observations indicate that classical, new, and atypical PKC isozymes are present in chick sympathetic neurons and that an atypical, phorbol ester-insensitive PKC is involved in the inhibition of voltage-activated calcium currents by α2-adrenoceptor activation.

the journal of neuroscience

Involvement of a Phorbol Ester-Insensitive Protein Kinase C in the α<sub>2</sub>-Adrenergic Inhibition of Voltage-Gated Calcium Current in Chick Sympathetic Neurons

Involvement of a Phorbol Ester-Insensitive Protein Kinase C in the α2-Adrenergic Inhibition of Voltage-Gated Calcium Current in Chick Sympathetic Neurons

Involvement of a Phorbol Ester-Insensitive Protein Kinase C in the α₂-Adrenergic Inhibition of Voltage-Gated Calcium Current in Chick Sympathetic Neurons