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Abstract:

1. The effects of the voltage-dependent calcium channel (VDCC) blockers ω-agatoxin IVA (ω-AgaIVA), ω-conotoxin GVIA (ω-CgTx), ω-conotoxin MVIIC (ω-MVIIC) and ω-conotoxin MVIID (ω-MVIID) were evaluated on transmitter release in the mouse diaphragm preparation. The effects of ω-AgaIVA and ω-MVIIC were also evaluated on the perineurial calcium and calcium-dependent potassium currents, I(ca), and I(K(Ca)), respectively, in the mouse levator auris preparation. 2. The P- and Q-type VDCC blocker ω-AgaIVA (100 nM) and P- Q- and N-type channel blockers ω-MVIIC (1 μM) and ω-MVIID (3 μM) strongly reduced transmitter release (> 80-90% blockade) whereas the selective N-type channel blocker ω-CgTx (5 μM) was ineffective. 3. The process of release was much more sensitive to ω-MVIIC (IC50 = 39 nM) than to ω-MVIID (IC50 = 1.4 μM). After almost completely blocking transmitter release (quantal content ~0.3% of its control value) with 3 μM ω-MVIIC, elevating the external [Ca2+] from 2 to 10 mM induced an increase of ~20 fold on the quantal content of the endplate potential (e.p.p.) (from 0.2 ± 0.04 to 4.8 ± 1.4). 4. Nerve-evoked transmitter release in a low Ca2+-high Mg2+ medium (low release probability, quantal content = 2 ± 0.1) had the same sensitivity to ω-AgaIVA (IC50 = 16.8 nM) as that in normal saline solutions. In addition, K+-evoked transmitter release was also highly sensitive to the action of this toxin (IC50 = 11.5 nM; 100 nM > 95% blockade). The action of ω-AgaIVA on transmitter release could be reversed by toxin washout if the experiments were carried out at 31-33°C. Conversely, the effect of ω-AgaIVA persisted even after two hours of toxin washout at room temperature. 5. Both the calcium and calcium-dependent potassium presynaptic currents, I(ca), and I(K(Ca)), respectively, were highly sensitive to low concentrations (10-30 nM) of ω-AgaIVA. The I(ca), and the I(K(Ca)) were also strongly reduced by 1 μM ω-MVIIC. The most marked difference between the action of these two toxins was the long incubation times required to achieve maximal effects with ω-MVIIC. 6. In summary these results provide more evidence that synaptic transmission at the mammalian neuromuscular junction is mediated by Ca2+ entry through P- and/or Q-type calcium channels.

Registro:

Documento: Artículo
Título:Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction
Autor:Katz, E.; Protti, D.A.; Ferro, P.A.; Rosato Siri, M.D.; Uchitel, O.D.
Filiación:Inst. Biol. Cel. y Neurociencias P., Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires (1121), Argentina
Departamento de Biología, Fac. de Ciencias Exactas y Naturales, Ciudad Universitaria, Buenos Aires (1428), Argentina
Instituto de Biología Celular, Facultad de Medicina, UBA, Paraquay 2155, (1121) Capital Federal, Argentina
Max Planck Inst. F. Biophysik. Chem., Am Fassberg, 37077 Goettingen, Germany
Palabras clave:ω-Agatoxin IVA; ω-conotoxin GVIA; ω-conotoxin MVIIC; ω-conotoxin MVIID; Calcium channel blockers; Calcium channels; Neuromuscular junction; Presynaptic currents; Synaptic transmission; Transmitter release; calcium channel; calcium channel blocking agent; calcium ion; neurotoxin; neurotransmitter; omega agatoxin IVA; omega conotoxin MVIIC; potassium; agents interacting with transmitter, hormone or drug receptors; calcium channel blocking agent; neurotoxin; omega conotoxin GVIA; peptide; potassium; potassium channel; spider venom; animal tissue; article; calcium transport; controlled study; diaphragm; endplate potential; male; mouse; neuromuscular synapse; neurotransmitter release; nonhuman; perineurium; potassium current; presynaptic nerve; priority journal; synaptic transmission; animal; drug effect; physiology; secretion; Animals; Calcium Channel Blockers; Calcium Channels; Male; Mice; Neuromuscular Junction; Neurotoxins; Neurotransmitter Agents; omega-Agatoxin IVA; omega-Conotoxin GVIA; Peptides; Potassium; Potassium Channels; Spider Venoms
Año:1997
Volumen:121
Número:8
Página de inicio:1531
Página de fin:1540
DOI: http://dx.doi.org/10.1038/sj.bjp.0701290
Título revista:British Journal of Pharmacology
Título revista abreviado:BR. J. PHARMACOL.
ISSN:00071188
CODEN:BJPCB
CAS:Calcium Channel Blockers; Calcium Channels; Neurotoxins; Neurotransmitter Agents; omega-Agatoxin IVA; omega-Conotoxin GVIA, 92078-76-7; Peptides; Potassium Channels; Potassium, 7440-09-7; Spider Venoms
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00071188_v121_n8_p1531_Katz.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00071188_v121_n8_p1531_Katz

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Citas:

---------- APA ----------
Katz, E., Protti, D.A., Ferro, P.A., Rosato Siri, M.D. & Uchitel, O.D. (1997) . Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction. British Journal of Pharmacology, 121(8), 1531-1540.
http://dx.doi.org/10.1038/sj.bjp.0701290
---------- CHICAGO ----------
Katz, E., Protti, D.A., Ferro, P.A., Rosato Siri, M.D., Uchitel, O.D. "Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction" . British Journal of Pharmacology 121, no. 8 (1997) : 1531-1540.
http://dx.doi.org/10.1038/sj.bjp.0701290
---------- MLA ----------
Katz, E., Protti, D.A., Ferro, P.A., Rosato Siri, M.D., Uchitel, O.D. "Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction" . British Journal of Pharmacology, vol. 121, no. 8, 1997, pp. 1531-1540.
http://dx.doi.org/10.1038/sj.bjp.0701290
---------- VANCOUVER ----------
Katz, E., Protti, D.A., Ferro, P.A., Rosato Siri, M.D., Uchitel, O.D. Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction. BR. J. PHARMACOL. 1997;121(8):1531-1540.
http://dx.doi.org/10.1038/sj.bjp.0701290