Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Acetazolamide (AZ), a molecule frequently used to treat different neurological syndromes, is an inhibitor of the carbonic anhydrase (CA), an enzyme that regulates pH inside and outside cells. We combined fluorescent FM styryl dyes and electrophysiological techniques at ex vivo levator auris longus neuromuscular junctions (NMJs) from mice to investigate the modulation of synaptic transmission and vesicle recycling by AZ. Transmitter release was minimally affected by AZ, as evidenced by evoked and spontaneous end-plate potential measurements. However, optical evaluation with FM-styryl dyes of vesicle exocytosis elicited by 50 Hz stimuli showed a strong reduction in fluorescence loss in AZ treated NMJ, an effect that was abolished by bathing the NMJ in Hepes. The remaining dye was quenched by bromophenol, a small molecule capable of diffusing inside vesicles. Furthermore, in transgenic mice expressing Synaptophysin-pHluorin (SypHy), the fluorescence responses of motor nerve terminals to a 50 Hz train of stimuli was decrease to a 50% of controls in the presence of AZ. Immunohistochemistry experiments to evaluate the state of the Myosin light chain kinase (MLCK), an enzyme involved in vesicle recycling, demonstrated that MLCK phosphorylation was much stronger in the presence than AZ than in its absence in 50 Hz stimulated NMJs. We postulate that AZ, via cytosol acidification and activation of MLCK, shifts synaptic vesicle recycling to a fast (kiss-and-run) mode, which changes synaptic performance. These changes may contribute to the therapeutic action reported in many neurological syndromes like ataxia, epilepsy, and migraine. © 2017 Wiley Periodicals, Inc.

Registro:

Documento: Artículo
Título:Carbonic anhydrase inhibitor acetazolamide shifts synaptic vesicle recycling to a fast mode at the mouse neuromuscular junction
Autor:Bertone, N.I.; Groisman, A.I.; Mazzone, G.L.; Cano, R.; Tabares, L.; Uchitel, O.D.
Filiación:Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET) and Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, C1428EHA, Argentina
Laboratorios de Investigación aplicada en Neurociencias (LIAN)—Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), CONICET, Buenos Aires, Argentina
Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, Seville, 41009, Spain
Palabras clave:bromophenol; endocytosis; endplate potentials; exocytosis; FM styryl dyes; myosin light chain kinase; synaptophysin-pHluorin; transmitter release; acetazolamide; bromophenol blue; dye; myosin light chain kinase; acetazolamide; carbonate dehydratase inhibitor; cardiac myosin; muscle relaxant agent; myosin light chain; myosin light chain 2; myosin light chain kinase; acidification; animal cell; animal tissue; Article; controlled study; endplate potential; enzyme activation; enzyme phosphorylation; evoked response; ex vivo study; exocytosis; fluorescence analysis; immunohistochemistry; male; motor end plate; mouse; neuromuscular junction; neurotransmitter release; nonhuman; priority journal; synapse vesicle; synaptic transmission; animal; C57BL mouse; cytology; cytosol; drug effects; membrane potential; metabolism; neuromuscular junction; pH; phosphorylation; physiology; synapse vesicle; transgenic mouse; Acetazolamide; Animals; Carbonic Anhydrase Inhibitors; Cardiac Myosins; Cytosol; Exocytosis; Hydrogen-Ion Concentration; Male; Membrane Potentials; Mice, Inbred C57BL; Mice, Transgenic; Myosin Light Chains; Myosin-Light-Chain Kinase; Neuromuscular Agents; Neuromuscular Junction; Phosphorylation; Synaptic Vesicles
Año:2017
Volumen:71
Número:12
DOI: http://dx.doi.org/10.1002/syn.22009
Título revista:Synapse
Título revista abreviado:Synapse
ISSN:08874476
CODEN:SYNAE
CAS:acetazolamide, 1424-27-7, 59-66-5; bromophenol blue, 115-39-9; myosin light chain kinase, 51845-53-5; muscle relaxant agent, 9008-44-0; Acetazolamide; Carbonic Anhydrase Inhibitors; Cardiac Myosins; myosin light chain 2; Myosin Light Chains; Myosin-Light-Chain Kinase; Neuromuscular Agents
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08874476_v71_n12_p_Bertone

Referencias:

  • Alés, E., Tabares, L., Poyato, J.M., Valero, V., Lindau, M., Alvarez de Toledo, G., High calcium concentrations shift the mode of exocytosis to the kiss-and-run mechanism (1999) Nature Cell Biology, 1 (1), pp. 40-44
  • Alvarez de Toledo, G., Fernández-Chacón, R., Fernández, J.M., Release of secretory products during transient vesicle fusion (1993) Nature, 363 (6429), pp. 554-558
  • Bagnato, F., Good, J., The use of antiepileptics in migraine prophylaxis (2016) Headache, 56 (3), pp. 603-615
  • Betz, W.J., Bewick, G.S., Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction (1992) Science 10, 255 (5041), pp. 200-203
  • Blumenthal, D.K., Stull, J.T., Effects of pH, ionic strength, and temperature on activation by calmodulin a catalytic activity of myosin light chain kinase (1982) Biochemistry, 21 (10), pp. 2386-2391
  • Breckenridge, L.J., Almers, W., Currents through the fusion pore that forms during exocytosis of a secretory vesicle (1987) Nature, 328, pp. 814-817
  • Bueno-Junior, L.S., Ruggiero, R.N., Rossignoli, M.T., Del Bel, E.A., Leite, J.P., Uchitel, O.D., Acetazolamide potentiates the afferent drive to prefrontal cortex in vivo (2017) Physiological Reports, 5 (1)
  • Cano, R., Ruiz, R., Shen, C., Tabares, L., Betz, W.J., The functional landscape of a presynaptic nerve terminal (2012) Cell Calcium, 52 (3-4), pp. 321-326
  • Ceccarelli, B., Hurlbut, W.P., Mauro, A., Depletion of vesicles from frog neuromuscular junctions by prolonged tetanic stimulation (1972) The Journal of Cell Biology, 54, pp. 30-38
  • Ceccarelli, B., Hurlbut, W.P., Mauro, A., Turnover of transmitter and synaptic vesicles at the frog neuromuscular junction (1973) The Journal of Cell Biology, 57, pp. 499-524
  • Davoust, J., Gruenberg, J., Howell, K.E., Two threshold values of low pH block endocytosis at different stages (1987) The Embo Journal, 6, pp. 3601-3609
  • Dejonghe, W., Kuenen, S., Mylle, E., Vasileva, M., Keech, O., Viotti, C., Russinova, E., Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification (2016) Nature Communications, 7, p. 11710
  • Fesce, R., Grohovaz, F., Valtorta, F., Meldolesi, J., Neurotransmitter release, fusion or ‘kiss and run’? (1994) Trends in Cell Biology, 4, pp. 1-4
  • Gaffield, M.A., Tabares, L., Betz, W.J., The spatial pattern of exocytosis and post-exocytic mobility of synaptopHluorin in mouse motor nerve terminals (2009) J Physiol, 587 (6), pp. 1187-1200
  • González-Forero, D., Montero, F., García-Morales, V., Domínguez, G., Gómez-Pérez, L., García-Verdugo, J.M., Moreno-López, B., Endogenous Rho-kinase signaling maintains synaptic strength by stabilizing the size of the readily releasable pool of synaptic vesicles (2012) The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 32 (1), pp. 68-84
  • Harata, N.C., Choi, S., Pyle, J.L., Aravanis, A.M., Tsien, R.W., Frequency dependent kinetics and prevalence of kiss and run and reuse at hippocampal synapses studied with novel quenching methods (2006) Neuron, 49 (2), pp. 243-256
  • Heuser, J.E., Effects of cytoplasmic acidification on clathrin lattice morphology (1989) The Journal of Cell Biology, 108, pp. 401-411
  • Heuser, J.E., Review of electron microscopic evidence favouring vesicle exocytosis as the structural basis for quantal release during synaptic transmission (1989) Quarterly Journal of Experimental Physiology, 74, pp. 1051-1069
  • He, L., Wu, L.G., The debate on the kiss-and-run fusion at synapses (2007) Trends Neurosci, 30 (9), pp. 447-455
  • Heuser, J.E., Reese, T.S., Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction (1973) The Journal of Cell Biology, 57, pp. 315-344
  • Hogan, B., Constantini, F., Lacey, E., (1994) Manipulating the mouse embryo: A laboratory manual, , Cold Spring Harbor, NY, Cold Spring Harbor Laboratory
  • Hoopmann, P., Rizzoli, S.O., Betz, W.J., Imaging synaptic vesicle recycling by staining and destaining vesicles with FM dyes (2012) Cold Spring Harbor Protocols, 2012 (1), pp. 77-83. , 1
  • Kaja, S., Frants, R.R., Ferrari, M.D., Van Den Maagdenberg, A.M., Plomp, J.J., Reduced ACh release at neuromuscular synapses of heterozygous leaner Ca(v)2.1-mutant mice (2008) Synapse (New York, N.Y.), 62 (5), pp. 337-344
  • Kotagal, V., Acetazolamide-responsive ataxia (2012) Seminars in Neurology, 32 (5), pp. 533-537
  • Kushmerick, C., Renden, R., Von, G.H., Physiological temperatures reduce the rate of vesicle pool depletion and short-term depression via an acceleration of vesicle recruitment (2006) Journal of Neuroscience, 26 (5), pp. 1366-1377
  • Li, L., Wu, X., Yue, H.Y., Zhu, Y.C., Xu, J., Myosin light chain kinase facilitates endocytosis of synaptic vesicles at hippocampal boutons (2016) Journal of Neurochemistry, 138 (1), pp. 60-73
  • Lindgren, C.A., Emery, D.G., Haydon, P.G., Intracellular acidification reversibly reduces endocytosis at the neuromuscular junction (1997) Journal of Neuroscience, 17, pp. 3074-3084
  • Maeno-Hikichi, Y., Polo-Parada, L., Kastanenka, K.V., Landmesser, L.T., Frequency-dependent modes of synaptic vesicle endocytosis and exocytosis at adult mouse neuromuscular junctions (2011) The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 31 (3), pp. 1093-1105
  • Maren, T.H., Carbonic anhydrase: Chemistry, physiology, and inhibition (1967) Physiological Reviews, 47 (4), pp. 595-781
  • McLachlan, E.M., Martin, A.R., Nonlinear summation of end-plate potentials in the frog and mouse (1981) The Journal of Physiology, 311, pp. 307-324
  • Ogawa, M., Pharmacological treatments of cerebellar ataxia (2004) Cerebellum (London, England), 3 (2), pp. 107-111
  • Perissinotti, P.P., Uchitel, O.D., Adenosine drives recycled vesicles to a slow-release pool at the mouse neuromuscular junction (2010) The European Journal of Neuroscience, 32 (6), pp. 985-996
  • Polo-Parada, L., Bose, C.M., Landmesser, L.T., Alterations in transmission, vesicle dynamics, and transmitter release machinery at NCAM-deficient neuromuscular junctions (2001) Neuron, 32 (5), pp. 815-828
  • Polo-Parada, L., Bose, C.M., Plattner, F., Landmesser, L.T., Distinct roles of different neural cell adhesion molecule (NCAM) isoforms in synaptic maturation revealed by analysis of NCAM 180 kDa isoform-deficient mice (2004) Journal of Neuroscience, (8), pp. 1852-1864. , 25, 24
  • Polo-Parada, L., Plattner, F., Bose, C., Landmesser, L.T., NCAM 180 acting via a conserved C-terminal domain and MLCK is essential for effective transmission with repetitive stimulation (2005) Neuron, 46 (6), pp. 917-931
  • Pyle, J.L., Kavalali, E.T., Piedras-Rentería, E.S., Tsien, R., Rapid reuse of readily releasable pool vesicles at hippocampal synapses (2000) Neuron, 28 (1), pp. 221-231
  • Renden, R., von Gersdorff, H., Synaptic vesicle endocytosis at a CNS nerve terminal: Faster kinetics at physiological temperatures and increased endocytotic capacity during maturation (2007) Journal of Neurophysiology, 98 (6), pp. 3349-3359
  • Ruiz, R., Cano, R., Casañas, J.J., Gaffield, M.A., Betz, W.J., Tabares, L., Active zones and the readily releasable pool of synaptic vesicles at the neuromuscular junction of the mouse (2011) Journal of Neuroscience, 31 (6), pp. 2000-2008
  • Ruusuvuori, E., Kaila, K., Carbonic anhydrases and brain pH in the control of neuronal excitability (2014) Subcellular Biochemistry, 75, pp. 271-290
  • Sandvig, K., Olsnes, S., Petersen, O.W., van Deurs, B., Acidification of the cytosol inhibits endocytosis from coated pits (1987) The Journal of Cell Biology, 105, pp. 679-689
  • Shaeki, Y., De Camilli, P., Synaptic vesicle endocytosis (2012) Cold Spring Harbor Perspectives in Biology, 4 (9), p. a005645
  • Srinivasan, G., Kim, J.H., von Gersdorff, H., The pool of fast releasing vesicles is augmented by myosin light chain kinase inhibition at the calyx of Held synapse (2008) Journal of Neurophysiology, 99 (4), pp. 1810-1824
  • Stevens, C.F., Williams, J.H., Kiss and run" exocytosis at hippocampal synapses (2000) Proceedings of the National Academy of Sciences of the United States of America, 97 (23), pp. 12828-12833
  • Tabares, L., Ruiz, R., Linares-Clemente, P., Gaffield, M.A., Alvarez de Toledo, G., Fernandez-Chacon, R., Betz, W.J., Monitoring synaptic function at the neuromuscular junction of a mouse expressing synaptopHluorin (2007) Journal of Neuroscience, 27, pp. 5422-5430
  • Wang, L.H., Südhof, T.C., Anderson, R.G., The appendage domain of alpha-adaptin is a high affinity binding site for dynamin (1995) The Journal of Biological Chemistry, 270, pp. 10079-10083
  • Yue, H.Y., Xu, J., Myosin light chain kinase accelerates vesicle endocytosis at the calyx of Held synapse (2014) The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 34 (1), pp. 295-304
  • Zhang, J., An, Y., Gao, J., Han, J., Pan, X., Pan, Y., Li, X., Aquaporin-1 translocation and degradation mediates the water transportation mechanism of acetazolamide (2012) Plos One, 7 (9)
  • Zhang, Q., Li, Y., Tsien, R.W., The dynamic control of kiss-and-run and vesicular reuse probed with single nanoparticles (2009) Science (New York, N.Y.), 323 (5920), pp. 1448-1453
  • Zhang, Z., Nguyen, K.T., Barrett, E.F., David, G., Vesicular ATPase inserted into the plasma membrane of motor terminals by exocytosis alkalinizes cytosolic pH and facilitates endocytosis (2010) Neuron, 68 (6), pp. 1097-1108

Citas:

---------- APA ----------
Bertone, N.I., Groisman, A.I., Mazzone, G.L., Cano, R., Tabares, L. & Uchitel, O.D. (2017) . Carbonic anhydrase inhibitor acetazolamide shifts synaptic vesicle recycling to a fast mode at the mouse neuromuscular junction. Synapse, 71(12).
http://dx.doi.org/10.1002/syn.22009
---------- CHICAGO ----------
Bertone, N.I., Groisman, A.I., Mazzone, G.L., Cano, R., Tabares, L., Uchitel, O.D. "Carbonic anhydrase inhibitor acetazolamide shifts synaptic vesicle recycling to a fast mode at the mouse neuromuscular junction" . Synapse 71, no. 12 (2017).
http://dx.doi.org/10.1002/syn.22009
---------- MLA ----------
Bertone, N.I., Groisman, A.I., Mazzone, G.L., Cano, R., Tabares, L., Uchitel, O.D. "Carbonic anhydrase inhibitor acetazolamide shifts synaptic vesicle recycling to a fast mode at the mouse neuromuscular junction" . Synapse, vol. 71, no. 12, 2017.
http://dx.doi.org/10.1002/syn.22009
---------- VANCOUVER ----------
Bertone, N.I., Groisman, A.I., Mazzone, G.L., Cano, R., Tabares, L., Uchitel, O.D. Carbonic anhydrase inhibitor acetazolamide shifts synaptic vesicle recycling to a fast mode at the mouse neuromuscular junction. Synapse. 2017;71(12).
http://dx.doi.org/10.1002/syn.22009