Stimulation of spontaneous transmitter release by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C.

Treatment of frog neuromuscular preparations with the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA) (100 nM) resulted in a 40% rise in the frequency of miniature endplate potentials (MEPPs) (P less than 0.05). When these experiments were repeated on preparations bathed in saline containing 10 mM K+ (a procedure that raises MEPP frequency by approximately 10-fold due to the elevated level of [Ca2+]i), TPA caused a 70-75% increase in MEPP frequency (P less than 0.02), although the data did not differ significantly from those recorded in standard frog saline due to the variability between preparations. It is concluded that transmitter release mechanisms may be modulated by protein kinase C and that such modulation probably acts synergistically with [Ca2+]i.