Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction
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...
Guardado en:
| Autores principales: | , , , , |
|---|---|
| Formato: | Artículo publishedVersion |
| Lenguaje: | Inglés |
| Publicado: |
1997
|
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00071188_v121_n8_p1531_Katz |
| Aporte de: |
| id |
paperaa:paper_00071188_v121_n8_p1531_Katz |
|---|---|
| record_format |
dspace |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| language |
Inglés |
| orig_language_str_mv |
eng |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
Artículo Artículo publishedVersion |
| author |
Katz, E. Protti, D.A. Ferro, P.A. Rosato Siri, M.D. Uchitel, O.D. |
| author_facet |
Katz, E. Protti, D.A. Ferro, P.A. Rosato Siri, M.D. Uchitel, O.D. |
| author_sort |
Katz, E. |
| title |
Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction |
| title_short |
Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction |
| title_full |
Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction |
| title_fullStr |
Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction |
| title_full_unstemmed |
Effects of Ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction |
| title_sort |
effects of ca2+ channel blocker neurotoxins on transmitter release and presynaptic currents at the mouse neuromuscular junction |
| publishDate |
1997 |
| url |
http://hdl.handle.net/20.500.12110/paper_00071188_v121_n8_p1531_Katz |
| work_keys_str_mv |
AT katze effectsofca2channelblockerneurotoxinsontransmitterreleaseandpresynapticcurrentsatthemouseneuromuscularjunction AT prottida effectsofca2channelblockerneurotoxinsontransmitterreleaseandpresynapticcurrentsatthemouseneuromuscularjunction AT ferropa effectsofca2channelblockerneurotoxinsontransmitterreleaseandpresynapticcurrentsatthemouseneuromuscularjunction AT rosatosirimd effectsofca2channelblockerneurotoxinsontransmitterreleaseandpresynapticcurrentsatthemouseneuromuscularjunction AT uchitelod effectsofca2channelblockerneurotoxinsontransmitterreleaseandpresynapticcurrentsatthemouseneuromuscularjunction |
| _version_ |
1769810311783645184 |
| spelling |
paperaa:paper_00071188_v121_n8_p1531_Katz2023-06-12T16:41:22Z 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 Katz, E. Protti, D.A. Ferro, P.A. Rosato Siri, M.D. Uchitel, O.D. 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 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. Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Protti, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rosato Siri, M.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Uchitel, O.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 1997 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00071188_v121_n8_p1531_Katz |