Intracellular injection of phorbol ester increases the excitability of neurons of the motor cortex of awake cats.

The electrophysiological effects of two intracellularly injected phorbol esters (PhEs) which activate protein kinase C, phorbol 12,13-dibutyrate and phorbol 12-myristate 13-acetate, were investigated in neurons of the motor cortex of awake cats. The major finding was that intracellularly injected PhEs increased the excitability of the neurons. This was indicated by (1) an increase in spontaneous firing and depolarizing current-induced spike activity, accompanied by a decrease in the latency and threshold of current-induced spike discharges, (2) a reduction in slow afterhyperpolarizations following action potentials and depolarizing pulses, and (3) the development of bursting activity. Neither increases in input resistance nor depolarization of the resting potential sufficient to account for these excitability changes were found. Increases in the amplitudes of action potentials and their fast afterhyperpolarizations were also observed. All changes occurred within 2-8 min after injection and lasted for 50 min or longer. Control injections of 4 alpha-phorbol 12,13-didecanoate, which does not activate protein kinase C, failed to induce changes in neuronal excitability or in any of the above parameters. We conclude that the excitability of neurons of the motor cortex of the awake cats can be increased by phorbol esters that translocate and activate protein kinase C.