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 unpaired median (DUM) neurons of the cockroach Periplaneta americana was investigated using the patch-clamp technique. The neuropeptide Neurohormone D (NHD), which belongs to the family of adipokinetic hormones, reversibly reduced 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) relation for peak currents by 23 +/- 6%. An analysis of NHD action on current kinetics in terms of the Hodgkin-Huxley formalism revealed that NHD reduces the time constant of inactivation, whereas steady-state activation and inactivation 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 mimicked the action of NHD. Furthermore, preincubation of cells with the protein 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. Activation 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 Gö 6976 did not essentially impair the NHD effects.
Wicher
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Sächsische Akademie der Wissenschaften zu Leipzig, D-07743 Jena, Germany. b6widi@pan.zoo.uni-jena.de
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007301:Insect Hormones / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010526:Periplaneta; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021122:Protein Subunits; D011930:Reaction Time / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D007301:Insect Hormones; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D021122:Protein Subunits; D015222:Sodium Channels; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C043192:glutamyl-valyl-asparaginyl-phenylalanyl-seryl-prolyl-asparaginyl-tryptophanamide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C