Effects of phorbol dibutyrate on M currents and M current inhibition in bullfrog sympathetic neurons

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Abstract
1. Effects of bath-applied phorbol dibutyrate (PDBu) on M currents (IM) and on the inhibition ofIM by muscarine and luteinizing hormone-releasing hormone (LHRH) were recorded in voltage-clamped bullfrog lumbar sympathetic ganglion cells. 2. PDBu (0.1–30µM) produced a slowly developing, irreversible and partial (⩽60%) inhibition ofIM. This effect was not replicated by 4-α-phorbol or by vehicle. 3. After treatment with PDBu, residualIM showed a reduced sensitivity to inhibition by muscarine or LHRH but not by Ba2+. The reduced response to muscarine appeared to result from a 10-fold shift in the concentration dependence for inhibition. 4. PDBu did not clearly reproduce the ability of muscarine to inhibit the slow, Ca-activated K currentIAHP or to increase the leak conductance at hyperpolarized potentials. The latter effect of muscarine was enhanced, rather than inhibited, by PDBu. 5. IM andIAHP were not inhibited by 1 mM dibutyryl cyclic AMP or by 20µM forskolin. 6. It is concluded that activation of protein kinase C, but not protein kinase A, partly replicates the effect of muscarine on frog sympathetic neurons.