Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Oct;87(20):8150–8154. doi: 10.1073/pnas.87.20.8150

Thyrotropin-releasing-hormone (TRH) and its physiological metabolite TRH-OH inhibit Na+ channel activity in mammalian septal neurons.

J López-Barneo 1, A Castellano 1, J Toledo-Aral 1
PMCID: PMC54910  PMID: 2172974

Abstract

The interaction of thyrotropin-releasing hormone (TRH) and its physiological metabolite TRH-OH with Na+ channels was studied in enzymatically dissociated guinea pig septal neurons by using the whole-cell variant of the patch-clamp technique. In about 60% of the cells tested, the neuropeptides at concentrations between 0.01 and 2.5 microM produced a dose-dependent reversible attenuation of Na+ currents. With 2 microM TRH-OH, peak Na+ current amplitude was reduced by 20-50% (27 +/- 8%, mean +/- SD; n = 16), whereas at the same concentration TRH was approximately half as effective as TRH-OH. In the presence of the tripeptides, the voltage-dependent parameter of the Na+ current were unaltered. TRH-induced reduction of Na+ current amplitude was transient and recovered almost completely during maintained exposure to the peptides. In addition, the response to either TRH-OH or TRH decreased with repeated treatment. Our results demonstrate that neuronal Na+ channels can be modulated by naturally occurring neuropeptides.

Full text

PDF
8150

Selected References

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

  1. Alvarez de Toledo G., López-Barneo J. Ionic basis of the differential neuronal activity of guinea-pig septal nucleus studied in vitro. J Physiol. 1988 Feb;396:399–415. doi: 10.1113/jphysiol.1988.sp016969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benham C. D. Voltage-gated and agonist-mediated rises in intracellular Ca2+ in rat clonal pituitary cells (GH3) held under voltage clamp. J Physiol. 1989 Aug;415:143–158. doi: 10.1113/jphysiol.1989.sp017716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bezanilla F., Armstrong C. M. Inactivation of the sodium channel. I. Sodium current experiments. J Gen Physiol. 1977 Nov;70(5):549–566. doi: 10.1085/jgp.70.5.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dekin M. S., Richerson G. B., Getting P. A. Thyrotropin-releasing hormone induces rhythmic bursting in neurons of the nucleus tractus solitarius. Science. 1985 Jul 5;229(4708):67–69. doi: 10.1126/science.3925552. [DOI] [PubMed] [Google Scholar]
  5. Dubinsky J. M., Oxford G. S. Dual modulation of K channels by thyrotropin-releasing hormone in clonal pituitary cells. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4282–4286. doi: 10.1073/pnas.82.12.4282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fernandez J. M., Fox A. P., Krasne S. Membrane patches and whole-cell membranes: a comparison of electrical properties in rat clonal pituitary (GH3) cells. J Physiol. 1984 Nov;356:565–585. doi: 10.1113/jphysiol.1984.sp015483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Hori T., Yamasaki M., Asami T., Koga H., Kiyohara T. Responses of anterior hypothalamic-preoptic thermosensitive neurons to thyrotropin releasing hormone and cyclo(His-Pro). Neuropharmacology. 1988 Sep;27(9):895–901. doi: 10.1016/0028-3908(88)90116-5. [DOI] [PubMed] [Google Scholar]
  9. Lamour Y., Senut M. C., Dutar P., Bassant M. H. Neuropeptides and septo-hippocampal neurons: electrophysiological effects and distributions of immunoreactivity. Peptides. 1988 Nov-Dec;9(6):1351–1359. doi: 10.1016/0196-9781(88)90202-1. [DOI] [PubMed] [Google Scholar]
  10. Levitan I. B. Modulation of ion channels in neurons and other cells. Annu Rev Neurosci. 1988;11:119–136. doi: 10.1146/annurev.ne.11.030188.001003. [DOI] [PubMed] [Google Scholar]
  11. Matteson D. R., Armstrong C. M. Na and Ca channels in a transformed line of anterior pituitary cells. J Gen Physiol. 1984 Mar;83(3):371–394. doi: 10.1085/jgp.83.3.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Morley J. E. Extrahypothalamic thyrotropin releasing hormone (TRH) -- its distribution and its functions. Life Sci. 1979 Oct 29;25(18):1539–1550. doi: 10.1016/0024-3205(79)90435-1. [DOI] [PubMed] [Google Scholar]
  13. Nicoll R. A. Excitatory action of TRH on spinal motoneurones. Nature. 1977 Jan 20;265(5591):242–243. doi: 10.1038/265242a0. [DOI] [PubMed] [Google Scholar]
  14. Reichlin S., Saperstein R., Jackson I. M., Boyd A. E., 3rd, Patel Y. Hypothalamic hormones. Annu Rev Physiol. 1976;38:389–424. doi: 10.1146/annurev.ph.38.030176.002133. [DOI] [PubMed] [Google Scholar]
  15. Renaud L. P., Blume H. W., Pittman Q. J., Lamour Y., Tan A. T. Thyrotropin-releasing hormone selectively depresses glutamate excitation of cerebral cortical neurons. Science. 1979 Sep 21;205(4412):1275–1277. doi: 10.1126/science.224461. [DOI] [PubMed] [Google Scholar]
  16. Renaud L. P., Martin J. B., Brazeau P. Depressant action of TRH, LH-RH and somatostatin on activity of central neurones. Nature. 1975 May 15;255(5505):233–235. doi: 10.1038/255233a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Schubert B., VanDongen A. M., Kirsch G. E., Brown A. M. Beta-adrenergic inhibition of cardiac sodium channels by dual G-protein pathways. Science. 1989 Aug 4;245(4917):516–519. doi: 10.1126/science.2547248. [DOI] [PubMed] [Google Scholar]
  19. Simasko S. M., Horita A. Localization of thyrotropin-releasing hormone (TRH) receptors in the septal nucleus of the rat brain. Brain Res. 1984 Apr 2;296(2):393–395. doi: 10.1016/0006-8993(84)90081-7. [DOI] [PubMed] [Google Scholar]
  20. Ureña J., López-López J., González C., López-Barneo J. Ionic currents in dispersed chemoreceptor cells of the mammalian carotid body. J Gen Physiol. 1989 May;93(5):979–999. doi: 10.1085/jgp.93.5.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ureña J., Mateos J. C., López-Barneo J. Low-cost system for automated acquisition, display and analysis of transmembrane ionic currents. Med Biol Eng Comput. 1989 Jan;27(1):94–98. doi: 10.1007/BF02442178. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES