Dynorphin A-Mediated Reduction in Multiple Calcium Currents Involves a Goa-Subtype G Protein in Rat Primary Afferent Neurons

Wiley, John W., Hylan C. Moises, Robert A. Gross, and Robert sensory afferent neurons and antagonize transmission of noL. Macdonald. Dynorphin A-mediated reduction in multiple calciceptive information entering CNS presumably via their cium currents involves a Goa-subtype G protein in rat primary action to reduce calcium currents. The N-type channels are afferent neurons. J. Neurophysiol. 77: 1338–1348, 1997. We exthought to provide the predominant target for inhibition by amined the effect of antisera directed at specific G-protein subopiates, as well as by a variety of other inhibitory neurotranstype(s) on dynorphin A (Dyn A)-mediated reduction of calcium mitters and neuromodulators (Anwyl 1991). However, recurrents in rat dorsal root ganglia (DRG) neurons. Whole cell cent studies have demonstrated modulation of P-type curpatch-clamp recordings were performed on acutely dissociated neurents by g-aminobutyric acid (Mintz and Bean 1993) and rons. Dyn A (1 mM)-mediated decrease in calcium currents was adenosine (Mogul et al. 1993) and suppression of Q-type inhibitedú90% by the preferential k-receptor antagonist norbinaltorphimine. Dyn A (300–1,000 nM)-mediated reduction in calcium currents by 1S, 3R-ACPD, carbachol, 2-chloroadenosine, currents was examined during intracellular administration of antiand baclofen (Wheeler et al. 1993). Thus it is possible that sera directed against specific regions of Goa , Gi1a/Gi2a , and Gi3a the depression of neurotransmitter release by opiates and subunits. Intracellular dialysis with an antiserum specific for Goa other inhibitory neuromodulators might occur through supfor 20 min decreased calcium current inhibition by Dyn A (1 mM) pression of activity of multiple types of high-threshold calin 13 of 15 neurons by an average of 75%. Dialysis with nonimcium channels. mune serum did not affect Dyn A’s action to reduce calcium curm-Opioid receptor activation decreases high-threshold, vrents. Intracellular dialysis with either anti-Gi1a/Gi2a or anti-Gi3a conotoxin-GVIA-sensitive (N-type) calcium current in antisera did not affect Dyn A-induced changes in calcium currents. acutely dissociated rat DRG neurons (Rusin and Moises In the presence of the N-type calcium channel antagonist v-cono1995). Furthermore m-agonists reduce a fraction of hightoxin GVIA, the P-type calcium channel antagonist v-Aga IVA, and v-Aga MVIIC applied subsequent to the other toxins, the effect threshold current that is resistant to blockade by saturating of Dyn A to reduce calcium currents was inhibited by 52, 28, and concentrations of v-GVIA and the L channel blocker nifedi16%, respectively. The L channel antagonist nifedipine did not pine (Rusin and Moises 1995). It is not known whether affect the ability of Dyn A to inhibit calcium currents. These results activation of k-opioid receptors has a similar or distinct acsuggest that in rat DRG neurons coupling of k-opioid receptors to tion on neuronal calcium currents. To characterize the calmultiple transient, high-threshold calcium currents involves the Goa cium channel types that might contribute to k-opioid-sensisubclass of G proteins. tive current, we examined the effects of application of the