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.
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Selected References
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- Bean B. P. Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6388–6392. doi: 10.1073/pnas.81.20.6388. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bean B. P. Two kinds of calcium channels in canine atrial cells. Differences in kinetics, selectivity, and pharmacology. J Gen Physiol. 1985 Jul;86(1):1–30. doi: 10.1085/jgp.86.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
- Bossu J. L., Feltz A., Thomann J. M. Depolarization elicits two distinct calcium currents in vertebrate sensory neurones. Pflugers Arch. 1985 Apr;403(4):360–368. doi: 10.1007/BF00589247. [DOI] [PubMed] [Google Scholar]
- Cachelin A. B., de Peyer J. E., Kokubun S., Reuter H. Ca2+ channel modulation by 8-bromocyclic AMP in cultured heart cells. Nature. 1983 Aug 4;304(5925):462–464. doi: 10.1038/304462a0. [DOI] [PubMed] [Google Scholar]
- Carbone E., Lux H. D. A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurones. Nature. 1984 Aug 9;310(5977):501–502. doi: 10.1038/310501a0. [DOI] [PubMed] [Google Scholar]
- Chang K. J., Cuatrecasas P. Multiple opiate receptors. Enkephalins and morphine bind to receptors of different specificity. J Biol Chem. 1979 Apr 25;254(8):2610–2618. [PubMed] [Google Scholar]
- Chavkin C., James I. F., Goldstein A. Dynorphin is a specific endogenous ligand of the kappa opioid receptor. Science. 1982 Jan 22;215(4531):413–415. doi: 10.1126/science.6120570. [DOI] [PubMed] [Google Scholar]
- Cherubini E., North R. A. Mu and kappa opioids inhibit transmitter release by different mechanisms. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1860–1863. doi: 10.1073/pnas.82.6.1860. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cognard C., Lazdunski M., Romey G. Different types of Ca2+ channels in mammalian skeletal muscle cells in culture. Proc Natl Acad Sci U S A. 1986 Jan;83(2):517–521. doi: 10.1073/pnas.83.2.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Deitmer J. W. Evidence for two voltage-dependent calcium currents in the membrane of the ciliate Stylonychia. J Physiol. 1984 Oct;355:137–159. doi: 10.1113/jphysiol.1984.sp015411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fedulova S. A., Kostyuk P. G., Veselovsky N. S. Two types of calcium channels in the somatic membrane of new-born rat dorsal root ganglion neurones. J Physiol. 1985 Feb;359:431–446. doi: 10.1113/jphysiol.1985.sp015594. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fields H. L., Emson P. C., Leigh B. K., Gilbert R. F., Iversen L. L. Multiple opiate receptor sites on primary afferent fibres. Nature. 1980 Mar 27;284(5754):351–353. doi: 10.1038/284351a0. [DOI] [PubMed] [Google Scholar]
- Fishman M. C., Spector I. Potassium current suppression by quinidine reveals additional calcium currents in neuroblastoma cells. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5245–5249. doi: 10.1073/pnas.78.8.5245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fox A. P., Krasne S. Two calcium currents in Neanthes arenaceodentatus egg cell membranes. J Physiol. 1984 Nov;356:491–505. doi: 10.1113/jphysiol.1984.sp015479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gilbert P. E., Martin W. R. The effects of morphine and nalorphine-like drugs in the nondependent, morphine-dependent and cyclazocine-dependent chronic spinal dog. J Pharmacol Exp Ther. 1976 Jul;198(1):66–82. [PubMed] [Google Scholar]
- Goldstein A., Fischli W., Lowney L. I., Hunkapiller M., Hood L. Porcine pituitary dynorphin: complete amino acid sequence of the biologically active heptadecapeptide. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7219–7223. doi: 10.1073/pnas.78.11.7219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldstein A., Tachibana S., Lowney L. I., Hunkapiller M., Hood L. Dynorphin-(1-13), an extraordinarily potent opioid peptide. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6666–6670. doi: 10.1073/pnas.76.12.6666. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hess P., Lansman J. B., Tsien R. W. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature. 1984 Oct 11;311(5986):538–544. doi: 10.1038/311538a0. [DOI] [PubMed] [Google Scholar]
- Hiller J. M., Simon E. J., Crain S. M., Peterson E. R. Opiate receptors in cultures of fetal mouse dorsal root ganglia (DRG) and spinal cord: predominance in DRG neurites. Brain Res. 1978 Apr 28;145(2):396–400. doi: 10.1016/0006-8993(78)90875-2. [DOI] [PubMed] [Google Scholar]
- Huidobro-Toro J. P., Yoshimura K., Lee N. M., Loh H. H., Way E. L. Dynorphin interaction at the kappa-opiate site. Eur J Pharmacol. 1981 Jun 19;72(2-3):265–266. doi: 10.1016/0014-2999(81)90284-3. [DOI] [PubMed] [Google Scholar]
- Kostyuk P. G., Veselovsky N. S., Fedulova S. A. Ionic currents in the somatic membrane of rat dorsal root ganglion neurons-II. Calcium currents. Neuroscience. 1981;6(12):2431–2437. doi: 10.1016/0306-4522(81)90089-0. [DOI] [PubMed] [Google Scholar]
- Lamotte C., Pert C. B., Snyder S. H. Opiate receptor binding in primate spinal cord: distribution and changes after dorsal root section. Brain Res. 1976 Aug 13;112(2):407–412. doi: 10.1016/0006-8993(76)90296-1. [DOI] [PubMed] [Google Scholar]
- Lord J. A., Waterfield A. A., Hughes J., Kosterlitz H. W. Endogenous opioid peptides: multiple agonists and receptors. Nature. 1977 Jun 9;267(5611):495–499. doi: 10.1038/267495a0. [DOI] [PubMed] [Google Scholar]
- Macdonald R. L., Werz M. A. Dynorphin A decreases voltage-dependent calcium conductance of mouse dorsal root ganglion neurones. J Physiol. 1986 Aug;377:237–249. doi: 10.1113/jphysiol.1986.sp016184. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martin W. R., Eades C. G., Thompson J. A., Huppler R. E., Gilbert P. E. The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther. 1976 Jun;197(3):517–532. [PubMed] [Google Scholar]
- Mihara S., North R. A. Opioids increase potassium conductance in submucous neurones of guinea-pig caecum by activating delta-receptors. Br J Pharmacol. 1986 Jun;88(2):315–322. doi: 10.1111/j.1476-5381.1986.tb10207.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mudge A. W., Leeman S. E., Fischbach G. D. Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration. Proc Natl Acad Sci U S A. 1979 Jan;76(1):526–530. doi: 10.1073/pnas.76.1.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nilius B., Hess P., Lansman J. B., Tsien R. W. A novel type of cardiac calcium channel in ventricular cells. Nature. 1985 Aug 1;316(6027):443–446. doi: 10.1038/316443a0. [DOI] [PubMed] [Google Scholar]
- Ninkovic M., Hunt S. P., Gleave J. R. Localization of opiate and histamine H1-receptors in the primate sensory ganglia and spinal cord. Brain Res. 1982 Jun 10;241(2):197–206. doi: 10.1016/0006-8993(82)91056-3. [DOI] [PubMed] [Google Scholar]
- North R. A., Katayama Y., Williams J. T. On the mechanism and site of action of enkephalin on single myenteric neurons. Brain Res. 1979 Apr 6;165(1):67–77. doi: 10.1016/0006-8993(79)90045-3. [DOI] [PubMed] [Google Scholar]
- North R. A., Tonini M. The mechanism of action of narcotic analgesics in the guinea-pig ileum. Br J Pharmacol. 1977 Dec;61(4):541–549. doi: 10.1111/j.1476-5381.1977.tb07546.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- North R. A., Williams J. T. Opiate activation of potassium conductance inhibits calcium action potentials in rat locus coeruleus neurones. Br J Pharmacol. 1983 Oct;80(2):225–228. doi: 10.1111/j.1476-5381.1983.tb10023.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nowycky M. C., Fox A. P., Tsien R. W. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature. 1985 Aug 1;316(6027):440–443. doi: 10.1038/316440a0. [DOI] [PubMed] [Google Scholar]
- Oka T., Negishi K., Suda M., Sawa A., Fujino M., Wakimasu M. Evidence that dynorphin-(1-13) acts as an agonist on opioid kappa-receptors. Eur J Pharmacol. 1982 Jan 22;77(2-3):137–141. doi: 10.1016/0014-2999(82)90008-5. [DOI] [PubMed] [Google Scholar]
- Pepper C. M., Henderson G. Opiates and opioid peptides hyperpolarize locus coeruleus neurons in vitro. Science. 1980 Jul 18;209(4454):394–395. doi: 10.1126/science.7384811. [DOI] [PubMed] [Google Scholar]
- Perney T. M., Hirning L. D., Leeman S. E., Miller R. J. Multiple calcium channels mediate neurotransmitter release from peripheral neurons. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6656–6659. doi: 10.1073/pnas.83.17.6656. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rane S. G., Dunlap K. Kinase C activator 1,2-oleoylacetylglycerol attenuates voltage-dependent calcium current in sensory neurons. Proc Natl Acad Sci U S A. 1986 Jan;83(1):184–188. doi: 10.1073/pnas.83.1.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ransom B. R., Christian C. N., Bullock P. N., Nelson P. G. Mouse spinal cord in cell culture. II. Synaptic activity and circuit behavior. J Neurophysiol. 1977 Sep;40(5):1151–1162. doi: 10.1152/jn.1977.40.5.1151. [DOI] [PubMed] [Google Scholar]
- Werz M. A., MacDonald R. L. Opioid peptides selective for mu- and delta-opiate receptors reduce calcium-dependent action potential duration by increasing potassium conductance. Neurosci Lett. 1983 Dec 2;42(2):173–178. doi: 10.1016/0304-3940(83)90402-0. [DOI] [PubMed] [Google Scholar]
- Werz M. A., Macdonald R. L. Dynorphin and neoendorphin peptides decrease dorsal root ganglion neuron calcium-dependent action potential duration. J Pharmacol Exp Ther. 1985 Jul;234(1):49–56. [PubMed] [Google Scholar]
- Werz M. A., Macdonald R. L. Dynorphin reduces calcium-dependent action potential duration by decreasing voltage-dependent calcium conductance. Neurosci Lett. 1984 May 4;46(2):185–190. doi: 10.1016/0304-3940(84)90439-7. [DOI] [PubMed] [Google Scholar]
- Werz M. A., Macdonald R. L. Dynorphin reduces voltage-dependent calcium conductance of mouse dorsal root ganglion neurons. Neuropeptides. 1984 Dec;5(1-3):253–256. doi: 10.1016/0143-4179(84)90075-1. [DOI] [PubMed] [Google Scholar]
- Werz M. A., Macdonald R. L. Heterogeneous sensitivity of cultured dorsal root ganglion neurones to opioid peptides selective for mu- and delta-opiate receptors. Nature. 1982 Oct 21;299(5885):730–733. doi: 10.1038/299730a0. [DOI] [PubMed] [Google Scholar]
- Werz M. A., Macdonald R. L. Opioid peptides decrease calcium-dependent action potential duration of mouse dorsal root ganglion neurons in cell culture. Brain Res. 1982 May 6;239(1):315–321. doi: 10.1016/0006-8993(82)90859-9. [DOI] [PubMed] [Google Scholar]
- Werz M. A., Macdonald R. L. Opioid peptides with differential affinity for mu and delta receptors decrease sensory neuron calcium-dependent action potentials. J Pharmacol Exp Ther. 1983 Nov;227(2):394–402. [PubMed] [Google Scholar]
- Werz M. A., Macdonald R. L. Phorbol esters: voltage-dependent effects on calcium-dependent action potentials of mouse central and peripheral neurons in cell culture. J Neurosci. 1987 Jun;7(6):1639–1647. doi: 10.1523/JNEUROSCI.07-06-01639.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams J. T., Egan T. M., North R. A. Enkephalin opens potassium channels on mammalian central neurones. Nature. 1982 Sep 2;299(5878):74–77. doi: 10.1038/299074a0. [DOI] [PubMed] [Google Scholar]
- Wüster M., Schulz R., Herz A. Opiate activity and receptor selectivity of dynorphin1-13 and related peptides. Neurosci Lett. 1980 Oct 20;20(1):79–83. doi: 10.1016/0304-3940(80)90237-2. [DOI] [PubMed] [Google Scholar]
- Yoshimura M., North R. A. Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature. 1983 Oct 6;305(5934):529–530. doi: 10.1038/305529a0. [DOI] [PubMed] [Google Scholar]
