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Abstract:

We studied the presynaptic muscarinic autoreceptor subtypes controlling ACh release and their relationship with voltage-dependent calcium channels in the neuromuscular synapses of the Levator auris longus muscle from adult (30-40 days) and newborn (3-6 and 15 days postnatal) rats. Using intracellular recording, we studied how several muscarinic antagonists affected the evoked endplate potentials. In some experiments we previously incubated the muscle with calcium channel blockers (nitrendipine, ω-conotoxin-GVIA and ω-Agatoxin-IVA) before determining the muscarinic response. In the adult, the M1 receptor-selective antagonist pirenzepine (10 μM) reduced evoked neurotransmission (≈47%). The M2 receptor-selective antagonist methoctramine (1 μM) increased the evoked release (≈67%). Both M1- and M2-mediated mechanisms depend on calcium influx via P/Q-type synaptic channels. We found nothing to indicate the presence of M3 (4-DAMP-sensitive) or M4 (tropicamide-sensitive) receptors in the muscles of adult or newborn rats. In the 3-6-day newborn rats, pirenzepine reduced the evoked release (≈30%) by a mechanism independent of L-, N- and P/Q-type calcium channels, and the M2 antagonist methoctramine (1 μM) unexpectedly decreased the evoked release (≈40%). This methoctramine effect was a P/Q-type calcium-channel-dependent mechanism. However, upon maturation in the first two postnatal weeks, the M2 pathway shifted to perform the calcium-dependent release-inhibitory activity found in the adult. We show that the way in which M1 and M2 muscarinic receptors modulate neurotransmission can differ between the developing and adult rat neuromuscular synapse.

Registro:

Documento: Artículo
Título:Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat
Autor:Santafé, M.M.; Salon, I.; Garcia, N.; Lanuza, M.A.; Uchitel, O.D.; Tomàs, J.
Filiación:Unitat d'Histologia i Neurobiologia, Facultat de Med. i C. de la S., Universitat Rovira i Virgili, carrer St Llorenç num 21, 43201-Reus, Spain
Lab. de Fisiol./Biol. Molec./Celular, Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428-Buenos Aires, Argentina
Palabras clave:Calcium channels; Cholinergic synapses; Motor end-plate; Motor nerve terminal; 1,1 dimethyl 4 diphenylacetoxypiperidinium iodide; acetylcholine; autoreceptor; calcium channel L type; calcium channel N type; calcium channel P type; calcium channel Q type; methoctramine; muscarinic M1 receptor; muscarinic M2 receptor; muscarinic M3 receptor; muscarinic M4 receptor; nitrendipine; omega agatoxin VIA; omega conotoxin GVIA; piperidine derivative; pirenzepine; tropicamide; unclassified drug; acetylcholine release; animal tissue; article; calcium transport; controlled study; dose response; drug effect; electrophysiology; miniature endplate potential; muscle contraction; neuromuscular synapse; neurotransmission; newborn; nonhuman; perinatal period; presynaptic nerve; priority journal; rat; Acetylcholine; Aging; Animals; Animals, Newborn; Autoreceptors; Calcium Channel Blockers; Calcium Channels; Calcium Channels, L-Type; Calcium Channels, N-Type; Calcium Channels, P-Type; Calcium Channels, Q-Type; Diamines; Electrophysiology; Motor Endplate; Muscarinic Antagonists; Muscle, Skeletal; Neuromuscular Junction; Nitrendipine; omega-Agatoxin IVA; omega-Conotoxin GVIA; Pirenzepine; Presynaptic Terminals; Rats; Rats, Sprague-Dawley; Receptor, Muscarinic M1; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptor, Muscarinic M4; Receptors, Muscarinic; Synaptic Transmission
Año:2003
Volumen:17
Número:1
Página de inicio:119
Página de fin:127
DOI: http://dx.doi.org/10.1046/j.1460-9568.2003.02428.x
Título revista:European Journal of Neuroscience
Título revista abreviado:Eur. J. Neurosci.
ISSN:0953816X
CODEN:EJONE
CAS:acetylcholine, 51-84-3, 60-31-1, 66-23-9; methoctramine, 104807-46-7; nitrendipine, 39562-70-4; omega conotoxin GVIA, 107407-86-3; pirenzepine, 28797-61-7, 29868-97-1; tropicamide, 1508-75-4; Acetylcholine, 51-84-3; Autoreceptors; Calcium Channel Blockers; Calcium Channels; Calcium Channels, L-Type; Calcium Channels, N-Type; Calcium Channels, P-Type; Calcium Channels, Q-Type; Diamines; methoctramine, 104807-46-7; Muscarinic Antagonists; Nitrendipine, 39562-70-4; omega-Agatoxin IVA; omega-Conotoxin GVIA, 92078-76-7; Pirenzepine, 28797-61-7; Receptor, Muscarinic M1; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptor, Muscarinic M4; Receptors, Muscarinic
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0953816X_v17_n1_p119_Santafe

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Citas:

---------- APA ----------
Santafé, M.M., Salon, I., Garcia, N., Lanuza, M.A., Uchitel, O.D. & Tomàs, J. (2003) . Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat. European Journal of Neuroscience, 17(1), 119-127.
http://dx.doi.org/10.1046/j.1460-9568.2003.02428.x
---------- CHICAGO ----------
Santafé, M.M., Salon, I., Garcia, N., Lanuza, M.A., Uchitel, O.D., Tomàs, J. "Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat" . European Journal of Neuroscience 17, no. 1 (2003) : 119-127.
http://dx.doi.org/10.1046/j.1460-9568.2003.02428.x
---------- MLA ----------
Santafé, M.M., Salon, I., Garcia, N., Lanuza, M.A., Uchitel, O.D., Tomàs, J. "Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat" . European Journal of Neuroscience, vol. 17, no. 1, 2003, pp. 119-127.
http://dx.doi.org/10.1046/j.1460-9568.2003.02428.x
---------- VANCOUVER ----------
Santafé, M.M., Salon, I., Garcia, N., Lanuza, M.A., Uchitel, O.D., Tomàs, J. Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat. Eur. J. Neurosci. 2003;17(1):119-127.
http://dx.doi.org/10.1046/j.1460-9568.2003.02428.x