Dual actions of phorbol esters to decrease calcium and potassium conductances of mouse neurons.

Phorbol esters, which substitute for diacylglycerol to activate protein kinase C, were applied to mouse dorsal root ganglion and cerebral hemisphere neurons in cell culture. The phorbol esters, phorbol 12,13-dibutyrate and 12-O-tetradecanoyl-phorbol-13-acetate, prolonged calcium-dependent action potential duration at resting membrane potential and at more negative membrane potentials but decreased action potential duration following membrane depolarization to less than -45 mV. When calcium and potassium currents were recorded using the single electrode voltage-clamp technique, the phorbol esters were shown to reduce both voltage-dependent calcium and potassium currents. These studies have demonstrated directly that phorbol esters, presumably by activating protein kinase C, can modify more than one membrane conductance in individual neurons.