Intracellular injection of protein kinase inhibitor blocks the serotonin-induced increase in K+ conductance in Aplysia neuron R15.

Previous work has shown that serotonin induces an increase in membrane K+ conductance in Aplysia neuron R15 and that this response is mediated by cAMP. The present study examines the role of protein phosphorylation in the response to serotonin. A specific inhibitor of cAMP-dependent protein kinase was injected intracellularly into neuron R15. The injection blocked the serotonin-induced increase in K+ conductance completely for at least 4 hours. The blockage was selective because the cell's response to dopamine was not inhibited. Furthermore, the blockage was specifically produced by protein kinase inhibitor because injection of other proteins (alpha-bungarotoxin and bovine serum albumin) did not affect the serotonin response. The serotonin response recovered fully 5-13 hours after the injection, presumably as a result of intracellular proteolysis of the protein kinase inhibitor. The results indicate that protein phosphorylation is a necessary step in the process that leads to activation of K+ channels by serotonin in neuron R15.