Carbonic anhydrase inhibitor acetazolamide shifts synaptic vesicle recycling to a fast mode at the mouse neuromuscular junction
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 n...
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John Wiley and Sons Inc.
2017
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| LEADER | 18359caa a22019337a 4500 | ||
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| 001 | PAPER-17414 | ||
| 003 | AR-BaUEN | ||
| 005 | 20230518204838.0 | ||
| 008 | 190410s2017 xx ||||fo|||| 00| 0 eng|d | ||
| 024 | 7 | |2 scopus |a 2-s2.0-85030125252 | |
| 024 | 7 | |2 cas |a 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 | |
| 040 | |a Scopus |b spa |c AR-BaUEN |d AR-BaUEN | ||
| 030 | |a SYNAE | ||
| 100 | 1 | |a Bertone, N.I. | |
| 245 | 1 | 0 | |a Carbonic anhydrase inhibitor acetazolamide shifts synaptic vesicle recycling to a fast mode at the mouse neuromuscular junction |
| 260 | |b John Wiley and Sons Inc. |c 2017 | ||
| 270 | 1 | 0 | |m Uchitel, O.D.; 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 UniversitariaArgentina; email: ouchitel@gmail.com |
| 506 | |2 openaire |e Política editorial | ||
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| 520 | 3 | |a 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. |l eng | |
| 536 | |a Detalles de la financiación: Agencia Nacional de Promoción Científica y Tecnológica, PICT-2011–2667, PICT 2013–2202 | ||
| 536 | |a Detalles de la financiación: Universidad de Buenos Aires, UBACYT 01/Q666, 20020130100666BA | ||
| 536 | |a Detalles de la financiación: Ministerio de Ciencia e Innovación | ||
| 536 | |a Detalles de la financiación: BFU2013-43763-P | ||
| 536 | |a Detalles de la financiación: Agencia Nacional de Promoción Científica y Tecnológica, UBACYT 01/Q666, 20020130100666BA | ||
| 536 | |a Detalles de la financiación: Universidad de Buenos Aires | ||
| 536 | |a Detalles de la financiación: Ministerio de Ciencia e Innovación | ||
| 536 | |a Detalles de la financiación: Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT), Grant number: PICT 2013–2202, PICT-2011–2667; Universidad de Buenos Aires, Grant number: UBACYT 01/Q666 (20020130100666BA); Spanish Ministry of Science and Innovation, Grant number: (MINECO/FEDER) BFU2013-43763-P | ||
| 536 | |a Detalles de la financiación: This work was supported by PICT 2013–2202 and PICT-2011–2667 from Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT) and UBACYT 01/Q666 (20020130100666BA) from Universidad de Buenos Aires (to Dr. Uchitel), and from the Spanish Ministry of Science and Innovation (MINECO/FEDER) BFU2013–43763-P (to Dr. Tabares). The authors thank María Eugenia Martin for her invaluable technical assistance. The authors declare no competing financial interests | ||
| 593 | |a 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 | ||
| 593 | |a Laboratorios de Investigación aplicada en Neurociencias (LIAN)—Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), CONICET, Buenos Aires, Argentina | ||
| 593 | |a Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, Seville, 41009, Spain | ||
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