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. 1993 Apr;463:17–38. doi: 10.1113/jphysiol.1993.sp019582

Serotonin inhibits Ca2+ currents in porcine melanotrophs by activating 5-HT1C and 5-HT1A receptors.

L Ciranna 1, D Mouginot 1, P Feltz 1, R Schlichter 1
PMCID: PMC1175331  PMID: 7504103

Abstract

1. We have investigated the effect of serotonin (5-HT) on Ca2+ currents in cultured porcine pituitary intermediate lobe (IL) cells. Electrophysiological recordings were performed in the whole-cell configuration of the patch-clamp technique. All membrane currents other than Ca2+ currents were blocked pharmacologically and by ionic substitution. 2. Two types of Ca2+ currents were recorded in IL cells, differing by their activation and inactivation properties. The first type of Ca2+ current was activated at membrane potentials more positive than -60 mV and had a transient time course during the 100 ms depolarizing voltage steps. The properties of this current correspond to those of the T-type or low-voltage-activated Ca2+ current. The second type of Ca2+ current had a threshold for activation between -30 and -20 mV and showed no sign of inactivation with time during the voltage steps. The properties of this current are similar to those of the L-type or high-voltage-activated Ca2+ current. 3. Current to voltage (I-V) relationships obtained either by conventional 100 ms voltage steps from a holding potential (VH) of -100 mV to various test potentials or by 800 ms voltage ramps from -100 to +50mV matched one another closely and showed two inward current humps corresponding to the activation of the T-type and L-type Ca2+ currents respectively. The ramp protocol was used to characterize the effect of 5-HT on the Ca2+ current I-V relationship. 4. 5-HT (100nM to 50 microM) reversibly inhibited the amplitude of the Ca2+ current triggered by 100 ms voltage jumps from a Vh of -100 mV to a test potential of 0 mV. 5. The effect of 5-HT was dose dependent with a threshold between 10 and 100 nM and a maximal effect at 10 microM. At a concentration of 10 microM, the average inhibition of Ca2+ current by 5-HT was 18.3 +/- 6.5% (n = 27). 5-HT inhibited Ba2+ current in a similar fashion. 6. When examining the effect of 5-HT on Ca2+ current I-V relationships, we observed a reversible inhibition of the high-threshold component corresponding to the L-type Ca2+ current. We never observed any effect of 5-HT on the T-type current. 7. The effect of 5-HT (10 microM) was antagonized to various extents by mianserin (1 microM) but not by ketanserin (0.1 microM), suggesting the involvement of 5-HT1C receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Berger A. J., Takahashi T. Serotonin enhances a low-voltage-activated calcium current in rat spinal motoneurons. J Neurosci. 1990 Jun;10(6):1922–1928. doi: 10.1523/JNEUROSCI.10-06-01922.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bockaert J., Fozard J. R., Dumuis A., Clarke D. E. The 5-HT4 receptor: a place in the sun. Trends Pharmacol Sci. 1992 Apr;13(4):141–145. doi: 10.1016/0165-6147(92)90051-7. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Canfield D. R., Dunlap K. Pharmacological characterization of amine receptors on embryonic chick sensory neurones. Br J Pharmacol. 1984 Jul;82(3):557–565. doi: 10.1111/j.1476-5381.1984.tb10794.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carbone E., Lux H. D. Kinetics and selectivity of a low-voltage-activated calcium current in chick and rat sensory neurones. J Physiol. 1987 May;386:547–570. doi: 10.1113/jphysiol.1987.sp016551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cota G. Calcium channel currents in pars intermedia cells of the rat pituitary gland. Kinetic properties and washout during intracellular dialysis. J Gen Physiol. 1986 Jul;88(1):83–105. doi: 10.1085/jgp.88.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Demeneix B. A., Taleb O., Loeffler J. P., Feltz P. GABAA and GABAB receptors on porcine pars intermedia cells in primary culture: functional role in modulating peptide release. Neuroscience. 1986 Apr;17(4):1275–1285. doi: 10.1016/0306-4522(86)90094-1. [DOI] [PubMed] [Google Scholar]
  8. Derkach V., Surprenant A., North R. A. 5-HT3 receptors are membrane ion channels. Nature. 1989 Jun 29;339(6227):706–709. doi: 10.1038/339706a0. [DOI] [PubMed] [Google Scholar]
  9. Douglas W. W., Taraskevich P. S. Calcium component to action potentials in rat pars intermedia cells. J Physiol. 1980 Dec;309:623–630. doi: 10.1113/jphysiol.1980.sp013530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fox A. P., Nowycky M. C., Tsien R. W. Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. J Physiol. 1987 Dec;394:149–172. doi: 10.1113/jphysiol.1987.sp016864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  12. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  13. Holz G. G., 4th, Shefner S. A., Anderson E. G. Serotonin decreases the duration of action potentials recorded from tetraethylammonium-treated bullfrog dorsal root ganglion cells. J Neurosci. 1986 Mar;6(3):620–626. doi: 10.1523/JNEUROSCI.06-03-00620.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hoyer D., Schoeffter P. 5-HT receptors: subtypes and second messengers. J Recept Res. 1991;11(1-4):197–214. doi: 10.3109/10799899109066399. [DOI] [PubMed] [Google Scholar]
  15. Jackson S., Lowry P. J. Secretion of pro-opiocortin peptides from isolated perfused rat pars intermedia cells. Neuroendocrinology. 1983 Oct;37(4):248–257. doi: 10.1159/000123553. [DOI] [PubMed] [Google Scholar]
  16. Keja J. A., Stoof J. C., Kits K. S. Voltage-activated currents through calcium channels in rat pituitary melanotrophic cells. Neuroendocrinology. 1991 Apr;53(4):349–359. doi: 10.1159/000125741. [DOI] [PubMed] [Google Scholar]
  17. Kleuss C., Hescheler J., Ewel C., Rosenthal W., Schultz G., Wittig B. Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. Nature. 1991 Sep 5;353(6339):43–48. doi: 10.1038/353043a0. [DOI] [PubMed] [Google Scholar]
  18. Kramer R. H., Kaczmarek L. K., Levitan E. S. Neuropeptide inhibition of voltage-gated calcium channels mediated by mobilization of intracellular calcium. Neuron. 1991 Apr;6(4):557–563. doi: 10.1016/0896-6273(91)90058-8. [DOI] [PubMed] [Google Scholar]
  19. Lamacz M., Tonon M. C., Leboulenger F., Héry F., Idres S., Verhofstad A. J., Pelletier G., Vaudry H. Effect of serotonin on alpha-melanocyte-stimulating hormone secretion from perifused frog neurointermediate lobe: evidence for the presence of serotonin-containing cells in the frog pars intermedia. J Endocrinol. 1989 Jul;122(1):135–146. doi: 10.1677/joe.0.1220135. [DOI] [PubMed] [Google Scholar]
  20. Léránth C., Palkovits M., Krieger D. T. Serotonin immunoreactive nerve fibers and terminals in the rat pituitary--light- and electron-microscopic studies. Neuroscience. 1983 Jun;9(2):289–296. doi: 10.1016/0306-4522(83)90294-4. [DOI] [PubMed] [Google Scholar]
  21. Mouginot D., Feltz P., Schlichter R. Modulation of GABA-gated chloride currents by intracellular Ca2+ in cultured porcine melanotrophs. J Physiol. 1991 Jun;437:109–132. doi: 10.1113/jphysiol.1991.sp018587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nomura Y., Kaneko S., Kato K., Yamagishi S., Sugiyama H. Inositol phosphate formation and chloride current responses induced by acetylcholine and serotonin through GTP-binding proteins in Xenopus oocyte after injection of rat brain messenger RNA. Brain Res. 1987 Jul;388(2):113–123. doi: 10.1016/s0006-8993(87)80004-5. [DOI] [PubMed] [Google Scholar]
  23. Palkovits M., Mezey E., Chiueh C. G., Krieger D. T., Gallatz K., Brownstein M. J. Serotonin-containing elements of the rat pituitary intermediate lobe. Neuroendocrinology. 1986;42(6):522–525. doi: 10.1159/000124497. [DOI] [PubMed] [Google Scholar]
  24. Paupardin-Tritsch D., Hammond C., Gerschenfeld H. M. Serotonin and cyclic GMP both induce an increase of the calcium current in the same identified molluscan neurons. J Neurosci. 1986 Sep;6(9):2715–2723. doi: 10.1523/JNEUROSCI.06-09-02715.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Penington N. J., Kelly J. S., Fox A. P. A study of the mechanism of Ca2+ current inhibition produced by serotonin in rat dorsal raphe neurons. J Neurosci. 1991 Nov;11(11):3594–3609. doi: 10.1523/JNEUROSCI.11-11-03594.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Penington N. J., Kelly J. S. Serotonin receptor activation reduces calcium current in an acutely dissociated adult central neuron. Neuron. 1990 May;4(5):751–758. doi: 10.1016/0896-6273(90)90201-p. [DOI] [PubMed] [Google Scholar]
  27. Randle J. C., Moor B. C., Kraicer J. Differential control of the release of pro-opiomelanocortin-derived peptides from the pars intermedia of the rat pituitary. Response to serotonin. Neuroendocrinology. 1983 Aug;37(2):131–140. doi: 10.1159/000123531. [DOI] [PubMed] [Google Scholar]
  28. Sano Y., Takeuchi Y., Matsuura T., Kawata M., Yamada H. Immunohistochemical demonstration of serotonin nerve fibers in the cat neurohypophysis. Histochemistry. 1982;75(3):293–299. doi: 10.1007/BF00496732. [DOI] [PubMed] [Google Scholar]
  29. Schultz G., Rosenthal W., Hescheler J., Trautwein W. Role of G proteins in calcium channel modulation. Annu Rev Physiol. 1990;52:275–292. doi: 10.1146/annurev.ph.52.030190.001423. [DOI] [PubMed] [Google Scholar]
  30. Scott R. H., Pearson H. A., Dolphin A. C. Aspects of vertebrate neuronal voltage-activated calcium currents and their regulation. Prog Neurobiol. 1991;36(6):485–520. doi: 10.1016/0301-0082(91)90014-r. [DOI] [PubMed] [Google Scholar]
  31. Stack J., Surprenant A. Dopamine actions on calcium currents, potassium currents and hormone release in rat melanotrophs. J Physiol. 1991 Aug;439:37–58. doi: 10.1113/jphysiol.1991.sp018655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stanley E. F., Russell J. T. Inactivation of calcium channels in rat pituitary intermediate lobe cells. Brain Res. 1988 Dec 13;475(1):64–72. doi: 10.1016/0006-8993(88)90199-0. [DOI] [PubMed] [Google Scholar]
  33. Taleb O., Trouslard J., Demeneix B. A., Feltz P. Characterization of calcium and sodium currents in porcine pars intermedia cells. Neurosci Lett. 1986 May 6;66(1):55–60. doi: 10.1016/0304-3940(86)90165-5. [DOI] [PubMed] [Google Scholar]
  34. Thayer S. A., Sturek M., Miller R. J. Measurement of neuronal Ca2+ transients using simultaneous microfluorimetry and electrophysiology. Pflugers Arch. 1988 Jul;412(1-2):216–223. doi: 10.1007/BF00583753. [DOI] [PubMed] [Google Scholar]
  35. Wang X., Treistman S. N., Lemos J. R. Two types of high-threshold calcium currents inhibited by omega-conotoxin in nerve terminals of rat neurohypophysis. J Physiol. 1992 Jan;445:181–199. doi: 10.1113/jphysiol.1992.sp018919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Williams P. J., MacVicar B. A., Pittman Q. J. Electrophysiological properties of neuroendocrine cells of the intact rat pars intermedia: multiple calcium currents. J Neurosci. 1990 Mar;10(3):748–756. doi: 10.1523/JNEUROSCI.10-03-00748.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Williams P. J., MacVicar B. A., Pittman Q. J. Synaptic modulation by dopamine of calcium currents in rat pars intermedia. J Neurosci. 1990 Mar;10(3):757–763. doi: 10.1523/JNEUROSCI.10-03-00757.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zhang Z. W., Feltz P. Nicotinic acetylcholine receptors in porcine hypophyseal intermediate lobe cells. J Physiol. 1990 Mar;422:83–101. doi: 10.1113/jphysiol.1990.sp017974. [DOI] [PMC free article] [PubMed] [Google Scholar]

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