Peptidergic modulation of an insect Na+ current: Role of protein kinase A and protein kinase C

The modulation of voltage-gated Na+ currents in isolated somata of dorsal u npaired median (DUM) neurons of the cockroach Periplaneta americana was inv estigated using the patch-clamp technique. The neuropeptide Neurohormone D (NHD), which belongs to the family of adipokinetic hormones, reversibly red uced the Na+ current in concentration-dependent manner (1 pM to 10 nM). At 10 nM, NHD caused an attenuation of the maximum of current-voltage (I-V) re lation for peak currents by 23 +/- 6%. An analysis of NHD action on current kinetics in terms of the Hodgkin-Huxley formalism revealed that NHD reduce s the time constant of inactivation, whereas steady-state activation and in activation as well as the time constant of activation were not affected. In addition, NHD prolonged the recovery from inactivation. The cAMP analogue 8-bromo-cAMP, forskolin, and the catalytic subunit of protein kinase A mimi cked the action of NHD. Furthermore, preincubation of cells with the protei n kinase A inhibitor KT 5720 abolished the action of NHD. Thus NHD seems to modify the Na+ current via channel phosphorylation by protein kinase A. Ac tivation of protein kinase C by oleoylacetylglycerol (OAG) also reduced the Na+ current, but it did not occlude the action of NHD. On the other hand, inhibition of protein kinase C by chelerythrine or Go 6976 did not essentia lly impair the NHD effects.