Abstract
1. Intracellular recordings were made from locus coeruleus (LC) neurones in a totally submerged brain slice preparation from adult rats. The effect of gamma-aminobutyric acid (GABA) on LC neurones was studied under current-clamp and voltage-clamp conditions. GABA caused inhibition of spontaneous firing and a large conductance increase in LC neurones. These effects could be accompanied by depolarization, hyperpolarization or little change in membrane potential depending on the presence or absence of Cl- in the recording microelectrode. 2. The reversal potential for GABA-induced changes in membrane potential (EGABA) was -71.3 +/- 1.1 mV (S.E.M., n = 21) in cells impaled with potassium acetate electrodes and -47.5 +/- 1.4 mV (S.E.M., n = 15) in cells impaled with KCl electrodes. When the external Cl- concentration was reduced EGABA was shifted in the depolarizing direction by 51.5 mV per tenfold change in external Cl- which is close to the shift predicted by the Nernst equation for a selective increase in CL- conductance. 3. GABA effects on LC neurones result from a direct action since they persist in low-Ca2+ and high-Mg2+ media which block synaptic transmission. 4. The effects of GABA were concentration dependent and antagonized by bicuculline (10 microM) and bicuculline methiodide (80-100 microM) indicating that they were mediated predominantly by an action on GABAA receptors. In the presence of bicuculline, EGABA was shifted towards the K+ equilibrium potential which indicated a residual bicuculline-resistant action at GABAB receptors. 5. GABA-induced responses were membrane potential dependent. GABA conductance was observed to decrease with membrane hyperpolarization in a linear manner. GABA-induced current showed outward rectification. In the voltage range studied (rest to -110 mV) the extent of this rectification was predicted by the Goldman-Hodgkin-Katz equation, suggesting that it was due to the unequal distribution of Cl- across the membrane. In addition, the time constant of decay of GABA current was decreased by membrane hyperpolarization; this could be due to a voltage-dependent change in receptor or channel kinetics. 6. These data suggest that the primary action of GABA on LC neurones is to increase Cl- conductance by activation of bicuculline-sensitive GABAA receptors. Due to the voltage dependence of GABA responses, GABA will exert a stronger inhibitory effect on LC neurones at depolarized than at hyperpolarized membrane potentials. This could serve as a negative feedback mechanism to control excitability of these neurones.
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- Adams P. R., Brown D. A. Actions of gamma-aminobutyric acid on sympathetic ganglion cells. J Physiol. 1975 Aug;250(1):85–120. doi: 10.1113/jphysiol.1975.sp011044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Adams P. R., Constanti A., Banks F. W. Voltage clamp analysis of inhibitory synaptic action in crayfish stretch receptor neurons. Fed Proc. 1981 Sep;40(11):2637–2641. [PubMed] [Google Scholar]
- Akaike N., Inomata N., Tokutomi N. Contribution of chloride shifts to the fade of gamma-aminobutyric acid-gated currents in frog dorsal root ganglion cells. J Physiol. 1987 Oct;391:219–234. doi: 10.1113/jphysiol.1987.sp016735. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alger B. E., Nicoll R. A. Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studied in vitro. J Physiol. 1982 Jul;328:125–141. doi: 10.1113/jphysiol.1982.sp014256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ashwood T. J., Collingridge G. L., Herron C. E., Wheal H. V. Voltage-clamp analysis of somatic gamma-aminobutyric acid responses in adult rat hippocampal CA1 neurones in vitro. J Physiol. 1987 Mar;384:27–37. doi: 10.1113/jphysiol.1987.sp016441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aston-Jones G., Ennis M., Pieribone V. A., Nickell W. T., Shipley M. T. The brain nucleus locus coeruleus: restricted afferent control of a broad efferent network. Science. 1986 Nov 7;234(4777):734–737. doi: 10.1126/science.3775363. [DOI] [PubMed] [Google Scholar]
- Barker J. L., Ransom B. R. Amino acid pharmacology of mammalian central neurones grown in tissue culture. J Physiol. 1978 Jul;280:331–354. doi: 10.1113/jphysiol.1978.sp012387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Belin M. F., Aguera M., Tappaz M., McRae-Degueurce A., Bobillier P., Pujol J. F. GABA-accumulating neurons in the nucleus raphe dorsalis and periaqueductal gray in the rat: a biochemical and radioautographic study. Brain Res. 1979 Jul 13;170(2):279–297. doi: 10.1016/0006-8993(79)90107-0. [DOI] [PubMed] [Google Scholar]
- Berod A., Chat M., Paut L., Tappaz M. Catecholaminergic and GABAergic anatomical relationship in the rat substantia nigra, locus coeruleus, and hypothalamic median eminence: immunocytochemical visualization of biosynthetic enzymes on serial semithin plastic-embedded sections. J Histochem Cytochem. 1984 Dec;32(12):1331–1338. doi: 10.1177/32.12.6150057. [DOI] [PubMed] [Google Scholar]
- Brown D. A., Scholfield C. N. Depolarization of neurones in the isolated olfactory cortex of the guinea-pig by gamma-aminobutyric acid. Br J Pharmacol. 1979 Feb;65(2):339–345. doi: 10.1111/j.1476-5381.1979.tb07835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cherubini E., North R. A., Williams J. T. Synaptic potentials in rat locus coeruleus neurones. J Physiol. 1988 Dec;406:431–442. doi: 10.1113/jphysiol.1988.sp017389. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collingridge G. L., Gage P. W., Robertson B. Inhibitory post-synaptic currents in rat hippocampal CA1 neurones. J Physiol. 1984 Nov;356:551–564. doi: 10.1113/jphysiol.1984.sp015482. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ennis M., Aston-Jones G. GABA-mediated inhibition of locus coeruleus from the dorsomedial rostral medulla. J Neurosci. 1989 Aug;9(8):2973–2981. doi: 10.1523/JNEUROSCI.09-08-02973.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gallagher J. P., Higashi H., Nishi S. Characterization and ionic basis of GABA-induced depolarizations recorded in vitro from cat primary afferent neurones. J Physiol. 1978 Feb;275:263–282. doi: 10.1113/jphysiol.1978.sp012189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gray R., Johnston D. Rectification of single GABA-gated chloride channels in adult hippocampal neurons. J Neurophysiol. 1985 Jul;54(1):134–142. doi: 10.1152/jn.1985.54.1.134. [DOI] [PubMed] [Google Scholar]
- Guyenet P. G., Aghajanian G. K. ACh, substance P and met-enkephalin in the locus coeruleus: pharmacological evidence for independent sites of action. Eur J Pharmacol. 1979 Feb 1;53(4):319–328. doi: 10.1016/0014-2999(79)90455-2. [DOI] [PubMed] [Google Scholar]
- HODGKIN A. L., KATZ B. The effect of sodium ions on the electrical activity of giant axon of the squid. J Physiol. 1949 Mar 1;108(1):37–77. doi: 10.1113/jphysiol.1949.sp004310. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamill O. P., Bormann J., Sakmann B. Activation of multiple-conductance state chloride channels in spinal neurones by glycine and GABA. 1983 Oct 27-Nov 2Nature. 305(5937):805–808. doi: 10.1038/305805a0. [DOI] [PubMed] [Google Scholar]
- Mason W. T., Poulain D., Cobbett P. gamma-Aminobutyric acid as an inhibitory neurotransmitter in the rat supraoptic nucleus: intracellular recordings in the hypothalamic slice. Neurosci Lett. 1987 Jan 27;73(3):259–265. doi: 10.1016/0304-3940(87)90255-2. [DOI] [PubMed] [Google Scholar]
- Newberry N. R., Nicoll R. A. Comparison of the action of baclofen with gamma-aminobutyric acid on rat hippocampal pyramidal cells in vitro. J Physiol. 1985 Mar;360:161–185. doi: 10.1113/jphysiol.1985.sp015610. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osmanović S. S., Shefner S. A. Anomalous rectification in rat locus coeruleus neurons. Brain Res. 1987 Aug 4;417(1):161–166. doi: 10.1016/0006-8993(87)90193-4. [DOI] [PubMed] [Google Scholar]
- Osmanović S. S., Shefner S. A. Baclofen increases the potassium conductance of rat locus coeruleus neurons recorded in brain slices. Brain Res. 1988 Jan 12;438(1-2):124–136. doi: 10.1016/0006-8993(88)91331-5. [DOI] [PubMed] [Google Scholar]
- Palacios J. M., Wamsley J. K., Kuhar M. J. High affinity GABA receptors-autoradiographic localization. Brain Res. 1981 Oct 19;222(2):285–307. doi: 10.1016/0006-8993(81)91034-9. [DOI] [PubMed] [Google Scholar]
- Pérez de la Mora M., Possani L. D., Tapia R., Teran L., Palacios R., Fuxe K., Hökfelt T., Ljungdahl A. Demonstration of central gamma-aminobutyrate-containing nerve terminals by means of antibodies against glutamate decarboxylase. Neuroscience. 1981;6(5):875–895. doi: 10.1016/0306-4522(81)90169-x. [DOI] [PubMed] [Google Scholar]
- Scharfman H. E., Sarvey J. M. Responses to gamma-aminobutyric acid applied to cell bodies and dendrites of rat visual cortical neurons. Brain Res. 1985 Dec 9;358(1-2):385–389. doi: 10.1016/0006-8993(85)90990-4. [DOI] [PubMed] [Google Scholar]
- Segal M., Barker J. L. Rat hippocampal neurons in culture: properties of GABA-activated Cl- ion conductance. J Neurophysiol. 1984 Mar;51(3):500–515. doi: 10.1152/jn.1984.51.3.500. [DOI] [PubMed] [Google Scholar]
- Shefner S. A., Chiu T. H. Adenosine inhibits locus coeruleus neurons: an intracellular study in a rat brain slice preparation. Brain Res. 1986 Feb 26;366(1-2):364–368. doi: 10.1016/0006-8993(86)91320-x. [DOI] [PubMed] [Google Scholar]
- Suzdak P. D., Gianutsos G. GABA-noradrenergic interaction: evidence for differential sites of action for GABA-A and GABA-B receptors. J Neural Transm. 1985;64(3-4):163–172. doi: 10.1007/BF01256464. [DOI] [PubMed] [Google Scholar]
- Weiss D. S., Barnes E. M., Jr, Hablitz J. J. Whole-cell and single-channel recordings of GABA-gated currents in cultured chick cerebral neurons. J Neurophysiol. 1988 Feb;59(2):495–513. doi: 10.1152/jn.1988.59.2.495. [DOI] [PubMed] [Google Scholar]
- Weiss D. S. Membrane potential modulates the activation of GABA-gated channels. J Neurophysiol. 1988 Feb;59(2):514–527. doi: 10.1152/jn.1988.59.2.514. [DOI] [PubMed] [Google Scholar]