Dynorphin A selectively reduces a large transient (N-type) calcium current of mouse dorsal root ganglion neurons in cell culture.
Opioid receptors are differentially coupled to ion channels. Mu- and delta-opioid receptors are coupled to calcium- and/or voltage-dependent potassium channels and kappa-opioid receptors are coupled to voltage-dependent calcium channels. Using the single-electrode voltage-clamp technique, we investigated the effect of the kappa-opioid receptor agonist dynorphin A on somatic calcium currents of mouse dorsal root ganglion (DRG) neurons in culture. Three different calcium currents were recorded: a small transient current activated positive to -60 mV; a large, inactivating current activated positive to -50 mV; and a moderate, slowly inactivating current activated positive to -40 mV. The first was less sensitive to cadmium block than the others. These calcium currents were similar to those described in other cells, which have been designated T, N, and L calcium currents, respectively. The opioid peptide dynorphin A reduced calcium current by selectively reducing the large inactivating (N) calcium current. Naloxone, an opioid receptor antagonist, reversed this action of dynorphin A. N calcium current is the predominant calcium current in DRG neurons. If N calcium channels are present in primary afferent terminals, and if they are coupled to kappa-opioid receptors as in the soma, these results suggest a mechanism by which dynorphin A inhibits calcium influx and neurotransmitter release.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004399:Dynorphins / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology*; D007473:Ion Channels / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011247:Pregnancy; D011957:Receptors, Opioid / Q000378:metabolism; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D007473:Ion Channels; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004399:Dynorphins; D011188:Potassium; D002118:Calcium