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Journal List > Proc Natl Acad Sci U S A > v.78(11); Nov 1981

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Proc Natl Acad Sci U S A. 1981 November; 78(11): 7180–7184.
PMCID: PMC349220
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Diazepam and (--)-pentobarbital: fluctuation analysis reveals different mechanisms for potentiation of gamma-aminobutyric acid responses in cultured central neurons.
R E Study and J L Barker
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Abstract
Diazepam and (--)-pentobarbital each potentiate the increase in chloride ion conductance produced by gamma-aminobutyric acid (GABA) i voltage-clamped mouse spinal neurons grown in culture. Fluctuation analysis was used to compare the properties of elementary ion-channel events underlying the chloride conductance produced by GABA alone and during potentiation by the two drugs. Neither drug altered the conductance of an open ion channel, but both drugs affected the kinetics of channel activity. Diazepam increased the frequency of channel openings and either did not affect or slightly increased the average open-channel lifetime, whereas (--)-pentobarbital decreased the frequency of channel openings and increased average open-channel lifetime. These changes in the kinetics of GABA-activated ion channels can quantitatively account for the potentiation of GABA responses observed with the drugs. Thus, the drugs each increase the response to GABA but do not act on channel kinetics in the same manner.
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
  • Costa E, Guidotti A. Molecular mechanisms in the receptor action of benzodiazepines. Annu Rev Pharmacol Toxicol. 1979;19:531–545. [PubMed]
  • ECCLES JC, SCHMIDT R, WILLIS WD. PHARMACOLOGICAL STUDIES ON PRESYNAPTIC INHIBITION. J Physiol. 1963 Oct;168:500–530. [PubMed]
  • Ransom BR, Barker JL. Pentobarbital modulates transmitter effects on mouse spinal neurones grown in tissue culture. Nature. 1975 Apr 24;254(5502):703–705. [PubMed]
  • Nicoll RA. Pentobarbital: action on frog motoneurons. Brain Res. 1975 Oct 10;96(1):119–123. [PubMed]
  • Macdonald R, Barker JL. Benzodiazepines specifically modulate GABA-mediated postsynaptic inhibition in cultured mammalian neurones. Nature. 1978 Feb 9;271(5645):563–564. [PubMed]
  • MacDonald RL, Barker JL. Enhancement of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of anticonvulsant action. Brain Res. 1979 May 11;167(2):323–336. [PubMed]
  • Barker JL, Ransom BR. Amino acid pharmacology of mammalian central neurones grown in tissue culture. J Physiol. 1978 Jul;280:331–354. [PubMed]
  • Barker JL, Ransom BR. Pentobarbitone pharmacology of mammalian central neurones grown in tissue culture. J Physiol. 1978 Jul;280:355–372. [PubMed]
  • McBurney RN, Barker JL. GABA-induced conductance fluctuations in cultured spinal neurones. Nature. 1978 Aug 10;274(5671):596–597. [PubMed]
  • Barker JL, McBurney RN. Phenobarbitone modulation of postsynaptic GABA receptor function on cultured mammalian neurons. Proc R Soc Lond B Biol Sci. 1979 Dec 31;206(1164):319–327. [PubMed]
  • Huang LY, Barker JL. Pentobarbital: stereospecific actions of (+) and (-) isomers revealed on cultured mammalian neurons. Science. 1980 Jan 11;207(4427):195–197. [PubMed]
  • Ransom BR, Neale E, Henkart M, Bullock PN, Nelson PG. Mouse spinal cord in cell culture. I. Morphology and intrinsic neuronal electrophysiologic properties. J Neurophysiol. 1977 Sep;40(5):1132–1150. [PubMed]
  • DeFelice LJ. Fluctuation analysis in neurobiology. Int Rev Neurobiol. 1977;20:169–208. [PubMed]
  • Neher E, Stevens CF. Conductance fluctuations and ionic pores in membranes. Annu Rev Biophys Bioeng. 1977;6:345–381. [PubMed]
  • Anderson CR, Stevens CF. Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction. J Physiol. 1973 Dec;235(3):655–691. [PubMed]
  • Ascher P, Marty A, Neild TO. Life time and elementary conductance of the channels mediating the excitatory effects of acetylcholine in Aplysia neurones. J Physiol. 1978 May;278:177–206. [PubMed]
  • Ascher P, Large WA, Rang HP. Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells. J Physiol. 1979 Oct;295:139–170. [PubMed]
  • Dudel J, Finger W, Stettmeier H. Inhibitory synaptic channels activated by gamma-aminobutyric acid (GABA) in crayfish muscle. Pflugers Arch. 1980 Sep;387(2):143–151. [PubMed]
  • Choi DW, Farb DH, Fischbach GD. Chlordiazepoxide selectively potentiates GABA conductance of spinal cord and sensory neurons in cell culture. J Neurophysiol. 1981 Apr;45(4):621–631. [PubMed]
  • Willow M, Johnston GA. Enhancement of GABA binding by pentobarbitone. Neurosci Lett. 1980 Jul;18(3):323–327. [PubMed]
  • MacDermott AB, Connor EA, Dionne VE, Parsons RL. Voltage clamp study of fast excitatory synaptic currents in bullfrog sympathetic ganglion cells. J Gen Physiol. 1980 Jan;75(1):39–60. [PubMed]
  • Faber DS, Korn H. Single-shot channel activation accounts for duration of inhibitory postsynaptic potentials in a central neuron. Science. 1980 May 9;208(4444):612–615. [PubMed]
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