Specific inhibitors of protein kinase C block transmitter-induced modulation of sensory neuron calcium current.

Modulation of neuronal, voltage-dependent calcium current has been described for a number of transmitters and peptides, but the biochemical basis for this phenomenon has not been completely identified. In several cases protein kinase C (PKC) is thought to mediate transmitter inhibition of calcium current; however, a lack of specific PKC inhibitors has hampered a direct physiological test of this idea. We have used the whole-cell, tight-seal configuration of the patch-clamp technique to apply intracellularly two specific PKC inhibitors to the cell bodies of embryonic chick sensory neurons. Both inhibitors, a 17 kd protein purified from bovine brain and a synthetic 13 amino acid "pseudosubstrate" peptide, blocked inhibition of calcium current by either norepinephrine or an exogenously applied PKC activator. These results provide strong evidence that activation of PKC is a prerequisite for the modulation of sensory neuron calcium current by norepinephrine.