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Published in: Journal of Anesthesia 5/2011

01-10-2011 | Original Article

Effects of propofol and pentobarbital on calcium concentration in presynaptic boutons on a rat hippocampal neuron

Authors: Shinichi Ito, Hitomi Sugiyama, Seiko Kitahara, Yoshimi Ikemoto, Takeshi Yokoyama

Published in: Journal of Anesthesia | Issue 5/2011

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Abstract

Purpose

Numerous reports suggest that intravenously administered (IV) anesthetics affect postsynaptic events in the central nervous system. However, there is little evidence about how general anesthetics influence the presynaptic processes. The level of presynaptic calcium (Ca2+) concentration ([Ca2+]pre) regulates neurotransmitter release. In this study, we investigated the effects of anesthetic propofol IV and the barbiturate pentobarbital on neurotransmitter release by measuring [Ca2+]pre in the presynaptic nerve terminals (boutons) on a dissociated single hippocampal rat neuron.

Methods

Sprague-Dawley rats 10–14 days old were decapitated under pentobarbital anesthesia, and brain slices were prepared. The hippocampal CA1 area was touched with a fire-polished glass pipette, which vibrated horizontally, and neurons were dissociated, along with the attached presynaptic boutons. The presynaptic boutons were visualized under a confocal laser-scanning microscope after staining with FM1-43 dye, and [Ca2+]pre was measured with acetoxymethyl ester of fluo-3 (fluo-3 AM).

Results

High potassium (K+) (15–90 mM) increased the [Ca2+]pre in the Ca2+-containing solution in a concentration-dependent manner. Whereas propofol (10 μM) and pentobarbital (300 μM) suppressed the high K+ (60 mM)-induced increase in [Ca2+]pre in the boutons attached to the dendrite, they did not affect [Ca2+]pre in the boutons attached to the soma or dendrite base. As a large majority of excitatory synapses are located on dendritic spines, these agents may affect Ca2+ mobilization in the excitatory presynaptic boutons.

Conclusions

Propofol and pentobarbital may affect neurotransmitter release from the excitatory presynaptic nerve terminals due to inhibition of increase in [Ca2+]pre.
Literature
1.
go back to reference Davies M, Thuynsma RP, Dunn SMJ. Effects of propofol and pentobarbital on ligand binding to GABAA receptors suggest a similar mechanism of action. Can J Physiol Pharmacol. 1998;76:46–52.PubMed Davies M, Thuynsma RP, Dunn SMJ. Effects of propofol and pentobarbital on ligand binding to GABAA receptors suggest a similar mechanism of action. Can J Physiol Pharmacol. 1998;76:46–52.PubMed
2.
go back to reference Mantz J, Lecharny JB, Laudenbach V, Henzel D, Peytavin G, Desmonts JM. Anesthetics affect the uptake but not the depolarization-evoked release of GABA in rat striatal synaptosomes. Anesthesiology. 1995;82:502–11.PubMedCrossRef Mantz J, Lecharny JB, Laudenbach V, Henzel D, Peytavin G, Desmonts JM. Anesthetics affect the uptake but not the depolarization-evoked release of GABA in rat striatal synaptosomes. Anesthesiology. 1995;82:502–11.PubMedCrossRef
3.
go back to reference Kitamura A, Sato R, Marszalec W, Yeh JZ, Ogawa R, Narahashi T. Halothane and propofol modulation of γ-aminobutyric acidA receptor single-channel currents. Anesth Analg. 2004;99:409–15.PubMedCrossRef Kitamura A, Sato R, Marszalec W, Yeh JZ, Ogawa R, Narahashi T. Halothane and propofol modulation of γ-aminobutyric acidA receptor single-channel currents. Anesth Analg. 2004;99:409–15.PubMedCrossRef
4.
go back to reference Orser BA, Wang LY, Pennefather PS, MacDonald JF. Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons. J Neurosci. 1994;14:7747–60.PubMed Orser BA, Wang LY, Pennefather PS, MacDonald JF. Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons. J Neurosci. 1994;14:7747–60.PubMed
5.
go back to reference Eghbali M, Gage PW, Birnir B. Effects of propofol on GABAA channel conductance in rat-cultured hippocampal neurons. Eur J Pharmacol. 2003;468:75–82.PubMedCrossRef Eghbali M, Gage PW, Birnir B. Effects of propofol on GABAA channel conductance in rat-cultured hippocampal neurons. Eur J Pharmacol. 2003;468:75–82.PubMedCrossRef
6.
go back to reference McDougall SJ, Bailey TW, Mendelowitz D, Andresen MC. Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS). Neuropharmacology. 2008;54:552–63.PubMedCrossRef McDougall SJ, Bailey TW, Mendelowitz D, Andresen MC. Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS). Neuropharmacology. 2008;54:552–63.PubMedCrossRef
7.
go back to reference Fisher MT, Fisher JL. Activation of α6-containing GABAA receptors by pentobarbital occurs through a different mechanism than activation by GABA. Neurosci Lett. 2010;471:195–9.PubMedCrossRef Fisher MT, Fisher JL. Activation of α6-containing GABAA receptors by pentobarbital occurs through a different mechanism than activation by GABA. Neurosci Lett. 2010;471:195–9.PubMedCrossRef
8.
go back to reference Frenkel C, Urban BW. Human brain sodium channels as one of the molecular target sites for the new intravenous anaesthetic propofol (2, 6-diisopropylphenol). Eur J Pharmacol. 1991;208:75–9.PubMedCrossRef Frenkel C, Urban BW. Human brain sodium channels as one of the molecular target sites for the new intravenous anaesthetic propofol (2, 6-diisopropylphenol). Eur J Pharmacol. 1991;208:75–9.PubMedCrossRef
9.
go back to reference Jones PJ, Wang Y, Smith MD, Hargus NJ, Eidam HS, White HS, Kapur J, Brown ML, Patel MK. Hydroxyamide analogs of propofol exhibit state-dependent block of sodium channels in hippocampal neurons: implications for anticonvulsant activity. J Pharmacol Exp Ther. 2007;320:828–36.PubMedCrossRef Jones PJ, Wang Y, Smith MD, Hargus NJ, Eidam HS, White HS, Kapur J, Brown ML, Patel MK. Hydroxyamide analogs of propofol exhibit state-dependent block of sodium channels in hippocampal neurons: implications for anticonvulsant activity. J Pharmacol Exp Ther. 2007;320:828–36.PubMedCrossRef
10.
go back to reference Kozinn J, Mao L, Arora A, Yang L, Fibuch EE, Wang JQ. Inhibition of glutamatergic activation of extracellular signal-regulated protein kinases in hippocampal neurons by the intravenous anesthetic propofol. Anesthesiology. 2006;105:1182–91.PubMedCrossRef Kozinn J, Mao L, Arora A, Yang L, Fibuch EE, Wang JQ. Inhibition of glutamatergic activation of extracellular signal-regulated protein kinases in hippocampal neurons by the intravenous anesthetic propofol. Anesthesiology. 2006;105:1182–91.PubMedCrossRef
11.
go back to reference Wei H, Xiong W, Yang S, Zhou Q, Liang C, Zeng BX, Xu L. Propofol facilitates the development of long-term depression (LTD) and impairs the maintenance of long-term potentiation (LTP) in the CA1 region of the hippocampus of anesthetized rats. Neurosci Lett. 2002;324:181–4.PubMedCrossRef Wei H, Xiong W, Yang S, Zhou Q, Liang C, Zeng BX, Xu L. Propofol facilitates the development of long-term depression (LTD) and impairs the maintenance of long-term potentiation (LTP) in the CA1 region of the hippocampus of anesthetized rats. Neurosci Lett. 2002;324:181–4.PubMedCrossRef
12.
go back to reference Zhang H, Wang W, Gao W, Ge Y, Zhang J, Wu S, Xu L. Effect of propofol on the levels of neurotransmitters in normal human brain: a magnetic resonance spectroscopy study. Neurosci Lett. 2009;467:247–51.PubMedCrossRef Zhang H, Wang W, Gao W, Ge Y, Zhang J, Wu S, Xu L. Effect of propofol on the levels of neurotransmitters in normal human brain: a magnetic resonance spectroscopy study. Neurosci Lett. 2009;467:247–51.PubMedCrossRef
13.
go back to reference Buggy DJ, Nicol B, Rowbotham DJ, Lambert DG. Effects of intravenous anesthetic agents on glutamate release: a role for GABAA receptor-mediated inhibition. Anesthesiology. 2000;92:1067–73.PubMedCrossRef Buggy DJ, Nicol B, Rowbotham DJ, Lambert DG. Effects of intravenous anesthetic agents on glutamate release: a role for GABAA receptor-mediated inhibition. Anesthesiology. 2000;92:1067–73.PubMedCrossRef
14.
go back to reference Jin YH, Zhang Z, Mendelowitz D, Andresen MC. Presynaptic actions of propofol enhance inhibitory synaptic transmission in isolated solitary tract nucleus neurons. Brain Res. 2009;1286:75–83.PubMedCrossRef Jin YH, Zhang Z, Mendelowitz D, Andresen MC. Presynaptic actions of propofol enhance inhibitory synaptic transmission in isolated solitary tract nucleus neurons. Brain Res. 2009;1286:75–83.PubMedCrossRef
15.
go back to reference Westphalen RI, Hemmings HC Jr. Selective depression by general anesthetics of glutamate versus GABA release from isolated cortical nerve terminals. J Pharmacol Exp Ther. 2003;304:1188–96.PubMedCrossRef Westphalen RI, Hemmings HC Jr. Selective depression by general anesthetics of glutamate versus GABA release from isolated cortical nerve terminals. J Pharmacol Exp Ther. 2003;304:1188–96.PubMedCrossRef
16.
go back to reference Kitayama M, Hirota K, Kudo M, Kudo T, Ishihara H, Matsuki A. Inhibitory effects of intravenous anaesthetic agents on K+-evoked glutamate release from rat cerebrocortical slices. Involvement of voltage-sensitive Ca2+ channels and GABAA receptors. Naunyn Schmiedebergs Arch Pharmacol. 2002;366:246–53.PubMedCrossRef Kitayama M, Hirota K, Kudo M, Kudo T, Ishihara H, Matsuki A. Inhibitory effects of intravenous anaesthetic agents on K+-evoked glutamate release from rat cerebrocortical slices. Involvement of voltage-sensitive Ca2+ channels and GABAA receptors. Naunyn Schmiedebergs Arch Pharmacol. 2002;366:246–53.PubMedCrossRef
17.
go back to reference Baudoux S, Empson RM, Richards CD. Pentobarbitone modulates calcium transients in axons and synaptic boutons of hippocampal CA1 neurons. Br J Pharmacol. 2003;140:971–9.PubMedCrossRef Baudoux S, Empson RM, Richards CD. Pentobarbitone modulates calcium transients in axons and synaptic boutons of hippocampal CA1 neurons. Br J Pharmacol. 2003;140:971–9.PubMedCrossRef
18.
go back to reference Richards CD. Anaesthetic modulation of synaptic transmission in the mammalian CNS. Br J Anaesth. 2002;89:79–90.PubMedCrossRef Richards CD. Anaesthetic modulation of synaptic transmission in the mammalian CNS. Br J Anaesth. 2002;89:79–90.PubMedCrossRef
19.
go back to reference Schneggenburger R, Nehr E. Presynaptic calcium and control of vesicle fusion. Curr Opin Neurobiol. 2005;15:266–74.PubMedCrossRef Schneggenburger R, Nehr E. Presynaptic calcium and control of vesicle fusion. Curr Opin Neurobiol. 2005;15:266–74.PubMedCrossRef
20.
go back to reference Llinás R, Sugimori M, Silver RB. Presynaptic calcium concentration microdomains and transmitter release. J Physiol Paris. 1992;86:135–8.PubMedCrossRef Llinás R, Sugimori M, Silver RB. Presynaptic calcium concentration microdomains and transmitter release. J Physiol Paris. 1992;86:135–8.PubMedCrossRef
21.
go back to reference Harata N, Wu J, Ishibashi H, Ono K, Akaike N. Rundown of the GABAA response under experimental ischemia in acutely dissociated CA1 pyramidal neurones of the rat. J Physiol. 1997;500:673–88.PubMed Harata N, Wu J, Ishibashi H, Ono K, Akaike N. Rundown of the GABAA response under experimental ischemia in acutely dissociated CA1 pyramidal neurones of the rat. J Physiol. 1997;500:673–88.PubMed
22.
go back to reference Akaike N, Murakami N, Katsurabayashi S, Jin YH, Imazawa T. Focal stimulation of single GABAergic presynaptic boutons on the rat hippocampal neuron. Neurosci Res. 2002;42:187–95.PubMedCrossRef Akaike N, Murakami N, Katsurabayashi S, Jin YH, Imazawa T. Focal stimulation of single GABAergic presynaptic boutons on the rat hippocampal neuron. Neurosci Res. 2002;42:187–95.PubMedCrossRef
23.
go back to reference Fukugasako S, Ito S, Ikemoto Y. Effects of methyl p-hydroxybenzoate (methyl paraben) on Ca2+ concentration and histamine release in rat peritoneal mast cells. Br J Pharmacol. 2003;139:381–7.PubMedCrossRef Fukugasako S, Ito S, Ikemoto Y. Effects of methyl p-hydroxybenzoate (methyl paraben) on Ca2+ concentration and histamine release in rat peritoneal mast cells. Br J Pharmacol. 2003;139:381–7.PubMedCrossRef
24.
go back to reference Lemke EA, Klingauf J. Single synaptic vesicle tracking in individual hippocampal boutons at rest and during synaptic activity. J Neurosci. 2005;25:11034–44.PubMedCrossRef Lemke EA, Klingauf J. Single synaptic vesicle tracking in individual hippocampal boutons at rest and during synaptic activity. J Neurosci. 2005;25:11034–44.PubMedCrossRef
25.
go back to reference Darrin H, Brager DH, Luther PW, Erdélyi F, Szabó G, Alger BE. Regulation of exocytosis from single visualized GABAergic boutons in hippocampal slices. J Neurosci. 2003;23:10475–86. Darrin H, Brager DH, Luther PW, Erdélyi F, Szabó G, Alger BE. Regulation of exocytosis from single visualized GABAergic boutons in hippocampal slices. J Neurosci. 2003;23:10475–86.
26.
go back to reference Takahashi T, Momiyama A. Different types of calcium channels mediate central synaptic transmission. Nature. 1993;366:156–8.PubMedCrossRef Takahashi T, Momiyama A. Different types of calcium channels mediate central synaptic transmission. Nature. 1993;366:156–8.PubMedCrossRef
27.
go back to reference Kim DK, Catterall WA. Ca2+-dependent and -independent interactions of the isoforms of the α1A subunit of brain Ca2+ channels with presynaptic SNARE proteins. Proc Natl Acad Sci USA. 1997;94:14782–6.PubMedCrossRef Kim DK, Catterall WA. Ca2+-dependent and -independent interactions of the isoforms of the α1A subunit of brain Ca2+ channels with presynaptic SNARE proteins. Proc Natl Acad Sci USA. 1997;94:14782–6.PubMedCrossRef
28.
go back to reference Robataille R, Adler EM, Charlton MP. Strategic location of calcium channels at transmitter release sites of frog neuromuscular synapses. Neuron. 1990;5:773–9.CrossRef Robataille R, Adler EM, Charlton MP. Strategic location of calcium channels at transmitter release sites of frog neuromuscular synapses. Neuron. 1990;5:773–9.CrossRef
29.
go back to reference Tibbs GR, Barrie AP, Van Mieghem FJE, McMahon HT, Nicholls DG. Repetitive action potentials in isolated nerve terminals in the presence of 4-aminopyridine: effects on cytosolic free Ca2+ and glutamate release. J Neurochem. 1989;53:1693–9.PubMedCrossRef Tibbs GR, Barrie AP, Van Mieghem FJE, McMahon HT, Nicholls DG. Repetitive action potentials in isolated nerve terminals in the presence of 4-aminopyridine: effects on cytosolic free Ca2+ and glutamate release. J Neurochem. 1989;53:1693–9.PubMedCrossRef
30.
go back to reference Leuner B, Falduto J, Shors TJ. Associative memory formation increases the observation of dendritic spines in the hippocampus. J Neurosci. 2003;23:659–65.PubMed Leuner B, Falduto J, Shors TJ. Associative memory formation increases the observation of dendritic spines in the hippocampus. J Neurosci. 2003;23:659–65.PubMed
31.
go back to reference Harris KM, Kater SB. Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function. Annu Rev Neurosci. 1994;17:341–71.PubMedCrossRef Harris KM, Kater SB. Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function. Annu Rev Neurosci. 1994;17:341–71.PubMedCrossRef
32.
go back to reference Eccles JC, Schmidt RF, Willis WD. Pharmacological studies of presynaptic inhibition. J Physiol. 1963;168:500–30.PubMed Eccles JC, Schmidt RF, Willis WD. Pharmacological studies of presynaptic inhibition. J Physiol. 1963;168:500–30.PubMed
33.
go back to reference Axmacher N, Winterer J, Stanton PK, Draguhn A, Müller W. Two-photon imaging of spontaneous vesicular release in acute brain slices and its modulation by presynaptic GABAA receptors. Neuro Image. 2004;22:1014–21.PubMed Axmacher N, Winterer J, Stanton PK, Draguhn A, Müller W. Two-photon imaging of spontaneous vesicular release in acute brain slices and its modulation by presynaptic GABAA receptors. Neuro Image. 2004;22:1014–21.PubMed
34.
go back to reference Fischer Y, Parnas I. Differential activation of two distinct mechanisms for presynaptic inhibition by a single inhibitory axon. J Neurophysiol. 1996;76:3807–16.PubMed Fischer Y, Parnas I. Differential activation of two distinct mechanisms for presynaptic inhibition by a single inhibitory axon. J Neurophysiol. 1996;76:3807–16.PubMed
35.
go back to reference Parnas I, Rashkovan G, Ravin R, Fischer Y. Novel mechanism for presynaptic inhibition: GABAA receptors affect the release machinery. J Neurophysiol. 2000;84:1240–6.PubMed Parnas I, Rashkovan G, Ravin R, Fischer Y. Novel mechanism for presynaptic inhibition: GABAA receptors affect the release machinery. J Neurophysiol. 2000;84:1240–6.PubMed
Metadata
Title
Effects of propofol and pentobarbital on calcium concentration in presynaptic boutons on a rat hippocampal neuron
Authors
Shinichi Ito
Hitomi Sugiyama
Seiko Kitahara
Yoshimi Ikemoto
Takeshi Yokoyama
Publication date
01-10-2011
Publisher
Springer Japan
Published in
Journal of Anesthesia / Issue 5/2011
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI
https://doi.org/10.1007/s00540-011-1186-4

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