Comparison of the action of baclofen with gamma-aminobutyric acid on rat hippocampal pyramidal cells in vitro (original) (raw)
Abstract
Intracellular recordings from CA1 pyramidal cells in the hippocampal slice preparation were used to compare the action of baclofen, a gamma-aminobutyric acid (GABA) analogue, with GABA. Ionophoretic application of GABA or baclofen into stratum (s.) pyramidale evoked hyperpolarizations associated with reductions in the input resistance of the cell. Baclofen responses were easier to elicit in the dendrites than in the cell body layer. Blockade of synaptic transmission, with tetrodotoxin or cadmium, did not reduce baclofen responses, indicating a direct post-synaptic action. (+)-Bicuculline (10 microM) and bicuculline methiodide (100 microM) had little effect on baclofen responses but strongly antagonized somatic GABA responses of equal amplitude. The bicuculline resistance of the baclofen response was not absolute, as higher concentrations of these compounds did reduce it. Pentobarbitone (100 microM) enhanced somatic GABA responses without affecting baclofen responses. (-)-Baclofen was approximately 200 times more potent than (+)-baclofen. The reversal potentials for the somatic GABA and baclofen responses were -70 mV and -85 mV respectively. When the membrane was depolarized, the baclofen response was reduced. This apparent voltage sensitivity was not seen with somatic GABA responses. Altering the chloride gradient across the cell membrane altered the reversal potential of the somatic GABA response but not that of the baclofen response. It was extrapolated that a tenfold shift in the extracellular potassium concentration would cause a 48 mV shift in the reversal potential of the baclofen response. Barium ions reduced the baclofen response, but not the GABA response. Orthodromic stimulation produced a fast inhibitory post-synaptic potential (i.p.s.p.) and a slow i.p.s.p. The properties of the fast and slow i.p.s.p.s were remarkably similar to those of the somatic GABA and baclofen responses, respectively. Application of GABA to the pyramidal cell dendrites evoked, in addition to a depolarization, two types of hyperpolarization. One type of hyperpolarization was bicuculline sensitive, had a reversal potential of about -65 mV and appeared to be chloride dependent. The other hyperpolarization was more easily observed in bicuculline methiodide (100 microM). This response was similar to that evoked by baclofen since it had a high reversal potential (about -90 mV), was relatively insensitive to changes in the chloride gradient across the cell membrane and was reduced by barium. The bicuculline-sensitive hyperpolarization could be evoked by the dendritic or somatic ionophoresis of muscimol and THIP (4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3(2H)-one.(ABSTRACT TRUNCATED AT 400 WORDS)
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- Aickin C. C., Deisz R. A., Lux H. D. Ammonium action on post-synaptic inhibition in crayfish neurones: implications for the mechanism of chloride extrusion. J Physiol. 1982 Aug;329:319–339. doi: 10.1113/jphysiol.1982.sp014305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Alger B. E., Nicoll R. A. Feed-forward dendritic inhibition in rat hippocampal pyramidal cells studied in vitro. J Physiol. 1982 Jul;328:105–123. doi: 10.1113/jphysiol.1982.sp014255. [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]
- Alger B. E., Nicoll R. A. Spontaneous inhibitory post-synaptic potentials in hippocampus: mechanism for tonic inhibition. Brain Res. 1980 Oct 27;200(1):195–200. doi: 10.1016/0006-8993(80)91108-7. [DOI] [PubMed] [Google Scholar]
- Allan R. D., Evans R. H., Johnston G. A. gamma-Aminobutyric acid agonists: an in vitro comparison between depression of spinal synaptic activity and depolarization of spinal root fibres in the rat. Br J Pharmacol. 1980 Dec;70(4):609–615. doi: 10.1111/j.1476-5381.1980.tb09779.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Andersen P., Dingledine R., Gjerstad L., Langmoen I. A., Laursen A. M. Two different responses of hippocampal pyramidal cells to application of gamma-amino butyric acid. J Physiol. 1980 Aug;305:279–296. doi: 10.1113/jphysiol.1980.sp013363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ault B., Nadler J. V. Baclofen selectively inhibits transmission at synapses made by axons of CA3 pyramidal cells in the hippocampal slice. J Pharmacol Exp Ther. 1982 Nov;223(2):291–297. [PubMed] [Google Scholar]
- Ault B., Nadler J. V. Effects of baclofen on synaptically-induced cell firing in the rat hippocampal slice. Br J Pharmacol. 1983 Sep;80(1):211–219. doi: 10.1111/j.1476-5381.1983.tb11068.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barker J. L., Ransom B. R. Pentobarbitone pharmacology of mammalian central neurones grown in tissue culture. J Physiol. 1978 Jul;280:355–372. doi: 10.1113/jphysiol.1978.sp012388. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ben-Ari Y., Krnjević K., Reiffenstein R. J., Reinhardt W. Inhibitory conductance changes and action of gamma-aminobutyrate in rat hippocampus. Neuroscience. 1981;6(12):2445–2463. doi: 10.1016/0306-4522(81)90091-9. [DOI] [PubMed] [Google Scholar]
- Bowery N. G., Doble A., Hill D. R., Hudson A. L., Shaw J. S., Turnbull M. J., Warrington R. Bicuculline-insensitive GABA receptors on peripheral autonomic nerve terminals. Eur J Pharmacol. 1981 Apr 24;71(1):53–70. doi: 10.1016/0014-2999(81)90386-1. [DOI] [PubMed] [Google Scholar]
- Bowery N. G., Hill D. R., Hudson A. L. Characteristics of GABAB receptor binding sites on rat whole brain synaptic membranes. Br J Pharmacol. 1983 Jan;78(1):191–206. doi: 10.1111/j.1476-5381.1983.tb09380.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bowery N. G., Hill D. R., Hudson A. L., Doble A., Middlemiss D. N., Shaw J., Turnbull M. (-)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor. Nature. 1980 Jan 3;283(5742):92–94. doi: 10.1038/283092a0. [DOI] [PubMed] [Google Scholar]
- Connors B. W., Gutnick M. J., Prince D. A. Electrophysiological properties of neocortical neurons in vitro. J Neurophysiol. 1982 Dec;48(6):1302–1320. doi: 10.1152/jn.1982.48.6.1302. [DOI] [PubMed] [Google Scholar]
- Constanti A., Connor J. D., Galvan M., Nistri A. Intracellularly-recorded effects of glutamate and aspartate on neurones in the guinea-pig olfactory cortex slice. Brain Res. 1980 Aug 18;195(2):403–420. doi: 10.1016/0006-8993(80)90075-x. [DOI] [PubMed] [Google Scholar]
- Curtis D. R., Johnston G. A. Amino acid transmitters in the mammalian central nervous system. Ergeb Physiol. 1974;69(0):97–188. doi: 10.1007/3-540-06498-2_3. [DOI] [PubMed] [Google Scholar]
- Davidoff R. A., Sears E. S. The effects of Lioresal on synaptic activity in the isolated spinal cord. Neurology. 1974 Oct;24(10):957–963. doi: 10.1212/wnl.24.10.957. [DOI] [PubMed] [Google Scholar]
- Davies J. Selective depression of synaptic excitation in cat spinal neurones by baclofen: an iontophoretic study. Br J Pharmacol. 1981 Feb;72(2):373–384. doi: 10.1111/j.1476-5381.1981.tb09137.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davies J., Watkins J. C. The action of beta-phenyl-GABA derivatives on neurones of the cat cerebral cortex. Brain Res. 1974 Apr 26;70(3):501–505. doi: 10.1016/0006-8993(74)90258-3. [DOI] [PubMed] [Google Scholar]
- Dodd J., Horn J. P. Muscarinic inhibition of sympathetic C neurones in the bullfrog. J Physiol. 1983 Jan;334:271–291. doi: 10.1113/jphysiol.1983.sp014494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dunlap K. Two types of gamma-aminobutyric acid receptor on embryonic sensory neurones. Br J Pharmacol. 1981 Nov;74(3):579–585. doi: 10.1111/j.1476-5381.1981.tb10467.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fox S., Krnjević K., Morris M. E., Puil E., Werman R. Action of baclofen on mammalian synaptic transmission. Neuroscience. 1978;3(6):495–515. doi: 10.1016/0306-4522(78)90016-7. [DOI] [PubMed] [Google Scholar]
- 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]
- Halliwell J. V., Adams P. R. Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res. 1982 Oct 28;250(1):71–92. doi: 10.1016/0006-8993(82)90954-4. [DOI] [PubMed] [Google Scholar]
- Heyer E. J., Nowak L. M., Macdonald R. L. Membrane depolarization and prolongation of calcium-dependent action potentials of mouse neurons in cell culture by two convulsants: bicuculline and penicillin. Brain Res. 1982 Jan 28;232(1):41–56. doi: 10.1016/0006-8993(82)90609-6. [DOI] [PubMed] [Google Scholar]
- Hotson J. R., Prince D. A. A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons. J Neurophysiol. 1980 Feb;43(2):409–419. doi: 10.1152/jn.1980.43.2.409. [DOI] [PubMed] [Google Scholar]
- Iversen L. L., Neal M. J. The uptake of [3H]GABA by slices of rat cerebral cortex. J Neurochem. 1968 Oct;15(10):1141–1149. doi: 10.1111/j.1471-4159.1968.tb06831.x. [DOI] [PubMed] [Google Scholar]
- Jahnsen H., Laursen A. M. The effects of a benzodiazepine on the hyperpolarizing and the depolarizing responses of hippocampal cells to GABA. Brain Res. 1981 Feb 23;207(1):214–217. doi: 10.1016/0006-8993(81)90696-x. [DOI] [PubMed] [Google Scholar]
- Jahr C. E., Nicoll R. A. An intracellular analysis of dendrodendritic inhibition in the turtle in vitro olfactory bulb. J Physiol. 1982 May;326:213–234. doi: 10.1113/jphysiol.1982.sp014187. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kehoe J. Ionic mechanisms of a two-component cholinergic inhibition in Aplysia neurones. J Physiol. 1972 Aug;225(1):85–114. doi: 10.1113/jphysiol.1972.sp009930. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kehoe J. Three acetylcholine receptors in Aplysia neurones. J Physiol. 1972 Aug;225(1):115–146. doi: 10.1113/jphysiol.1972.sp009931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knutsson E., Lindblom U., Mårtensson A. Plasma and cerebrospinal fluid levels of baclofen (Lioresal) at optimal therapeutic responses in spastic paresis. J Neurol Sci. 1974 Nov;23(3):473–484. doi: 10.1016/0022-510x(74)90163-4. [DOI] [PubMed] [Google Scholar]
- Lancaster B., Wheal H. V. The synaptically evoked late hyperpolarisation in hippocampal CA1 pyramidal cells is resistant to intracellular EGTA. Neuroscience. 1984 May;12(1):267–275. doi: 10.1016/0306-4522(84)90152-0. [DOI] [PubMed] [Google Scholar]
- 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]
- Marder E., Paupardin-Tritsch D. The pharmacological properties of some crustacean neuronal acetylcholine, gamma-aminobutyric acid, and L-glutamate responses. J Physiol. 1978 Jul;280:213–236. doi: 10.1113/jphysiol.1978.sp012381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Meyer H. The different actions of chloride and potassium on postsynaptic inhibition of an isolated neurone. J Exp Biol. 1976 Apr;64(2):477–487. doi: 10.1242/jeb.64.2.477. [DOI] [PubMed] [Google Scholar]
- Mori K., Nowycky M. C., Shepherd G. M. Analysis of a long-duration inhibitory potential in mitral cells in the isolated turtle olfactory bulb. J Physiol. 1981 May;314:311–320. doi: 10.1113/jphysiol.1981.sp013709. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Newberry N. R., Nicoll R. A. A bicuculline-resistant inhibitory post-synaptic potential in rat hippocampal pyramidal cells in vitro. J Physiol. 1984 Mar;348:239–254. doi: 10.1113/jphysiol.1984.sp015107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Newberry N. R., Nicoll R. A. Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. 1984 Mar 29-Apr 4Nature. 308(5958):450–452. doi: 10.1038/308450a0. [DOI] [PubMed] [Google Scholar]
- Nicoll R. A., Alger B. E. A simple chamber for recording from submerged brain slices. J Neurosci Methods. 1981 Aug;4(2):153–156. doi: 10.1016/0165-0270(81)90049-2. [DOI] [PubMed] [Google Scholar]
- Nicoll R. A., Alger B. E. Synaptic excitation may activate a calcium-dependent potassium conductance in hippocampal pyramidal cells. Science. 1981 May 22;212(4497):957–959. doi: 10.1126/science.6262912. [DOI] [PubMed] [Google Scholar]
- Nicoll R. A. Pentobarbital: action on frog motoneurons. Brain Res. 1975 Oct 10;96(1):119–123. doi: 10.1016/0006-8993(75)90582-x. [DOI] [PubMed] [Google Scholar]
- Olpe H. R., Baudry M., Fagni L., Lynch G. The blocking action of baclofen on excitatory transmission in the rat hippocampal slice. J Neurosci. 1982 Jun;2(6):698–703. doi: 10.1523/JNEUROSCI.02-06-00698.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olpe H. R., Demiéville H., Baltzer V., Bencze W. L., Koella W. P., Wolf P., Haas H. L. The biological activity of d- and l-baclofen (Lioresal). Eur J Pharmacol. 1978 Nov 1;52(1):133–136. doi: 10.1016/0014-2999(78)90032-8. [DOI] [PubMed] [Google Scholar]
- Olsen R. W., Snowman A. M. [3H]bicuculline methochloride binding to low-affinity gamma-aminobutyric acid receptor sites. J Neurochem. 1983 Dec;41(6):1653–1663. doi: 10.1111/j.1471-4159.1983.tb00877.x. [DOI] [PubMed] [Google Scholar]
- Pierau F. K., Zimmermann P. Action of a GABA-derivative on postsynaptic potentials and membrane properties of cats' spinal motoneurones. Brain Res. 1973 May 17;54:376–380. doi: 10.1016/0006-8993(73)90064-4. [DOI] [PubMed] [Google Scholar]
- Pong S. F., Graham L. T., Jr A simple preparation of bicuculline methiodide, a water-soluble GABA antagonist. Brain Res. 1973 Aug 17;58(1):266–267. doi: 10.1016/0006-8993(73)90844-5. [DOI] [PubMed] [Google Scholar]
- Satou M., Mori K., Tazawa Y., Takagi S. F. Two types of postsynaptic inhibition in pyriform cortex of the rabbit: fast and slow inhibitory postsynaptic potentials. J Neurophysiol. 1982 Nov;48(5):1142–1156. doi: 10.1152/jn.1982.48.5.1142. [DOI] [PubMed] [Google Scholar]
- Schwartzkroin P. A., Stafstrom C. E. Effects of EGTA on the calcium-activated afterhyperpolarization in hippocampal CA3 pyramidal cells. Science. 1980 Dec 5;210(4474):1125–1126. doi: 10.1126/science.6777871. [DOI] [PubMed] [Google Scholar]
- Shimizu N., Akaike N., Oomura Y., Maruhashi J., Klee M. R. GABA and lioresal actions on the identified Onchidium neuron. Jpn J Physiol. 1983;33(3):459–467. doi: 10.2170/jjphysiol.33.459. [DOI] [PubMed] [Google Scholar]
- Simmonds M. A. Classification of some GABA antagonists with regard to site of action and potency in slices of rat cuneate nucleus. Eur J Pharmacol. 1982 Jun 4;80(4):347–358. doi: 10.1016/0014-2999(82)90080-2. [DOI] [PubMed] [Google Scholar]
- Somogyi P., Smith A. D., Nunzi M. G., Gorio A., Takagi H., Wu J. Y. Glutamate decarboxylase immunoreactivity in the hippocampus of the cat: distribution of immunoreactive synaptic terminals with special reference to the axon initial segment of pyramidal neurons. J Neurosci. 1983 Jul;3(7):1450–1468. doi: 10.1523/JNEUROSCI.03-07-01450.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thalmann R. H., Ayala G. F. A late increase in potassium conductance follows synaptic stimulation of granule neurons of the dentate gyrus. Neurosci Lett. 1982 Apr 26;29(3):243–248. doi: 10.1016/0304-3940(82)90324-x. [DOI] [PubMed] [Google Scholar]
- Thalmann R. H., Peck E. J., Ayala G. F. Biphasic response of hippocampal pyramidal neurons to GABA. Neurosci Lett. 1981 Feb 6;21(3):319–324. doi: 10.1016/0304-3940(81)90224-x. [DOI] [PubMed] [Google Scholar]
- Thalmann R. H. Reversal properties of an EGTA-resistant late hyperpolarization that follows synaptic stimulation of hippocampal neurons. Neurosci Lett. 1984 Apr 20;46(1):103–108. doi: 10.1016/0304-3940(84)90206-4. [DOI] [PubMed] [Google Scholar]
- Yarowsky P. J., Carpenter D. O. Receptors for gamma-aminobutyric acid (GABA) on Aplysia neurons. Brain Res. 1978 Apr 7;144(1):75–94. doi: 10.1016/0006-8993(78)90436-5. [DOI] [PubMed] [Google Scholar]