Dynorphin A selectively reduces a large transient (N-type) calcium current of mouse dorsal root ganglion neurons in cell culture

Abstract

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.