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. 1986 Jun;375:481–497. doi: 10.1113/jphysiol.1986.sp016129

Prolongation of calcium action potentials by gamma-aminobutyric acid in primary sensory neurones of lamprey.

J P Leonard, W O Wickelgren
PMCID: PMC1182771  PMID: 2432226

Abstract

Intracellular recordings from primary mechanosensory neurones (dorsal cells) in the lamprey spinal cord were used to test the membrane effects of a variety of putative neuromodulatory agents. gamma-Aminobutyric acid (GABA) produced a dose-dependent increase in the duration of mixed Na-Ca or pure Ca action potentials in these cells. L-Glutamate and glycine produced minimal broadening of Ca action potentials. Acetylcholine, noradrenaline, serotonin, met-enkephalin, D-glutamate and dopamine had no effect. The pharmacology of GABA's action appeared to be complex. While the GABAA receptor antagonists, bicuculline, picrotoxin and curare, did not block GABA's effect, both the GABAA receptor agonist, muscimol, and the GABAB-receptor agonist, baclofen, occasionally broadened Ca action potentials in these cells. GABA had no effect on the resting potential, passive current-voltage (I-V) characteristics and pure Na action potential of dorsal cells, ruling out an action on passive membrane channels, transmitter-activated channels, or on those voltage-dependent channels activated during the Na action potential. Thus, GABA affected dorsal cells only when a significant Ca current was evident. GABA appeared not to increase the conductance of the Ca channels since its action was accompanied by an increase in input resistance, suggesting an inhibition of Ca-dependent conductance that normally acts to repolarize the membrane during a Ca action potential. An inhibitory effect of GABA on a Ca-dependent Cl conductance was ruled out in experiments where the Cl gradient was altered by removal of extracellular Cl without affecting GABA-induced Ca action potential prolongation. Dorsal cells have a prominent Ca-dependent K conductance (gK(Ca], and it is this conductance that GABA may inhibit. Consistent with this was the observation that the hyperpolarizing after-potential that follows Ca action potentials in dorsal cells, which reflects gK(Ca) in these cells and whose duration is normally increased when the Ca action potential duration increases, was not prolonged when the Ca action potential was broadened by GABA. Further, the failure of GABA to prolong Ba action potentials was consistent with this proposed mechanism of action, since Ba apparently does not activate gK(Ca) in these cells. Forskolin, a specific adenylate cyclase activator, caused broadening of Ca action potentials in lamprey dorsal cells comparable in magnitude to that of GABA. Thus, an increase in intracellular cyclic AMP is a candidate for the intracellular mediator of GABA's effect on these cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alger B. E., Nicoll R. A. Epileptiform burst afterhyperolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science. 1980 Dec 5;210(4474):1122–1124. doi: 10.1126/science.7444438. [DOI] [PubMed] [Google Scholar]
  2. Bader C. R., Bertrand D., Schwartz E. A. Voltage-activated and calcium-activated currents studied in solitary rod inner segments from the salamander retina. J Physiol. 1982 Oct;331:253–284. doi: 10.1113/jphysiol.1982.sp014372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bixby J. L., Spitzer N. C. Enkephalin reduces calcium action potentials in Rohon-Beard neurons in vivo. J Neurosci. 1983 May;3(5):1014–1018. doi: 10.1523/JNEUROSCI.03-05-01014.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dunlap K., Fischbach G. D. Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones. J Physiol. 1981 Aug;317:519–535. doi: 10.1113/jphysiol.1981.sp013841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dunlap K. Forskolin prolongs action potential duration and blocks potassium current in embryonic chick sensory neurons. Pflugers Arch. 1985 Feb;403(2):170–174. doi: 10.1007/BF00584096. [DOI] [PubMed] [Google Scholar]
  6. Galvan M., Adams P. R. Control of calcium current in rat sympathetic neurons by norepinephrine. Brain Res. 1982 Jul 22;244(1):135–144. doi: 10.1016/0006-8993(82)90911-8. [DOI] [PubMed] [Google Scholar]
  7. Gorman A. L., Hermann A. Internal effects of divalent cations on potassium permeability in molluscan neurones. J Physiol. 1979 Nov;296:393–410. doi: 10.1113/jphysiol.1979.sp013012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grafe P., Mayer C. J., Wood J. D. Synaptic modulation of calcium-dependent potassium conductance in myenteric neurones in the guinea-pig. J Physiol. 1980 Aug;305:235–248. doi: 10.1113/jphysiol.1980.sp013360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Haas H. L., Konnerth A. Histamine and noradrenaline decrease calcium-activated potassium conductance in hippocampal pyramidal cells. 1983 Mar 31-Apr 6Nature. 302(5907):432–434. doi: 10.1038/302432a0. [DOI] [PubMed] [Google Scholar]
  10. Hagiwara S., Byerly L. Calcium channel. Annu Rev Neurosci. 1981;4:69–125. doi: 10.1146/annurev.ne.04.030181.000441. [DOI] [PubMed] [Google Scholar]
  11. Homma S., Rovainen C. M. Conductance increases produced by glycine and gamma-aminobutyric acid in lamprey interneurones. J Physiol. 1978 Jun;279:231–252. doi: 10.1113/jphysiol.1978.sp012342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Horn J. P., McAfee D. A. Alpha-drenergic inhibition of calcium-dependent potentials in rat sympathetic neurones. J Physiol. 1980 Apr;301:191–204. doi: 10.1113/jphysiol.1980.sp013198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kandel E. R., Schwartz J. H. Molecular biology of learning: modulation of transmitter release. Science. 1982 Oct 29;218(4571):433–443. doi: 10.1126/science.6289442. [DOI] [PubMed] [Google Scholar]
  14. Kilmer S. L., Carlsen R. C. Forskolin activation of adenylate cyclase in vivo stimulates nerve regeneration. Nature. 1984 Feb 2;307(5950):455–457. doi: 10.1038/307455a0. [DOI] [PubMed] [Google Scholar]
  15. Leonard J. P., Wickelgren W. O. Calcium spike and calcium-dependent potassium conductance in mechanosensory neurons of the lamprey. J Neurophysiol. 1985 Jan;53(1):171–182. doi: 10.1152/jn.1985.53.1.171. [DOI] [PubMed] [Google Scholar]
  16. Madison D. V., Nicoll R. A. Noradrenaline blocks accommodation of pyramidal cell discharge in the hippocampus. Nature. 1982 Oct 14;299(5884):636–638. doi: 10.1038/299636a0. [DOI] [PubMed] [Google Scholar]
  17. Martin A. R., Wickelgren W. O., Ber1anek R. Effects of iontophoretically applied drugs on spinal interneurons of the lamprey. J Physiol. 1970 May;207(3):653–665. doi: 10.1113/jphysiol.1970.sp009086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Martin A. R., Wickelgren W. O. Sensory cells in the spinal cord of the sea lamprey. J Physiol. 1971 Jan;212(1):65–83. doi: 10.1113/jphysiol.1971.sp009310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Matthews G., Wickelgren W. O. Glycine, GABA and synaptic inhibition of reticulospinal neurones of lamprey. J Physiol. 1979 Aug;293:393–415. doi: 10.1113/jphysiol.1979.sp012896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Meech R. W., Thomas R. C. Effect of measured calcium chloride injections on the membrane potential and internal pH of snail neurones. J Physiol. 1980 Jan;298:111–129. doi: 10.1113/jphysiol.1980.sp013070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. North R. A., Tokimasa T. Depression of calcium-dependent potassium conductance of guinea-pig myenteric neurones by muscarinic agonists. J Physiol. 1983 Sep;342:253–266. doi: 10.1113/jphysiol.1983.sp014849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Osterrieder W., Brum G., Hescheler J., Trautwein W., Flockerzi V., Hofmann F. Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current. Nature. 1982 Aug 5;298(5874):576–578. doi: 10.1038/298576a0. [DOI] [PubMed] [Google Scholar]
  23. Owen D. G., Segal M., Barker J. L. A Ca-dependent Cl- conductance in cultured mouse spinal neurones. Nature. 1984 Oct 11;311(5986):567–570. doi: 10.1038/311567a0. [DOI] [PubMed] [Google Scholar]
  24. Reuter H. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature. 1983 Feb 17;301(5901):569–574. doi: 10.1038/301569a0. [DOI] [PubMed] [Google Scholar]
  25. Reuter H. The dependence of slow inward current in Purkinje fibres on the extracellular calcium-concentration. J Physiol. 1967 Sep;192(2):479–492. doi: 10.1113/jphysiol.1967.sp008310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Romey G., Lazdunski M. The coexistence in rat muscle cells of two distinct classes of Ca2+-dependent K+ channels with different pharmacological properties and different physiological functions. Biochem Biophys Res Commun. 1984 Jan 30;118(2):669–674. doi: 10.1016/0006-291x(84)91355-x. [DOI] [PubMed] [Google Scholar]
  27. Rovainen C. M. Synaptic interactions of identified nerve cells in the spinal cord of the sea lamprey. J Comp Neurol. 1974 Mar 15;154(2):189–206. doi: 10.1002/cne.901540206. [DOI] [PubMed] [Google Scholar]
  28. Seamon K. B., Padgett W., Daly J. W. Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3363–3367. doi: 10.1073/pnas.78.6.3363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Siegelbaum S. A., Camardo J. S., Kandel E. R. Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones. Nature. 1982 Sep 30;299(5882):413–417. doi: 10.1038/299413a0. [DOI] [PubMed] [Google Scholar]
  30. Tsien R. W., Giles W., Greengard P. Cyclic AMP mediates the effects of adrenaline on cardiac purkinje fibres. Nat New Biol. 1972 Dec 6;240(101):181–183. doi: 10.1038/newbio240181a0. [DOI] [PubMed] [Google Scholar]
  31. Vassort G., Rougier O., Garnier D., Sauviat M. P., Coraboeuf E., Gargouïl Y. M. Effects of adrenaline on membrane inward currents during the cardiac action potential. Pflugers Arch. 1969;309(1):70–81. doi: 10.1007/BF00592283. [DOI] [PubMed] [Google Scholar]
  32. Wald U., Selzer M. E., Krieger N. R. Glutamic acid decarboxylase in sea lamprey (Petromyzon marinus): characterization, localization, and developmental changes. J Neurochem. 1981 Feb;36(2):363–368. doi: 10.1111/j.1471-4159.1981.tb01603.x. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. 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]

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