Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat
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 intracellula...
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todo:paper_0953816X_v17_n1_p119_Santafe2023-10-03T15:51:16Z Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat Santafé, M.M. Salon, I. Garcia, N. Lanuza, M.A. Uchitel, O.D. Tomàs, J. 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 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. Fil:Uchitel, O.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0953816X_v17_n1_p119_Santafe |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Santafé, M.M. Salon, I. Garcia, N. Lanuza, M.A. Uchitel, O.D. Tomàs, J. |
| author_facet |
Santafé, M.M. Salon, I. Garcia, N. Lanuza, M.A. Uchitel, O.D. Tomàs, J. |
| author_sort |
Santafé, M.M. |
| title |
Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat |
| title_short |
Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat |
| title_full |
Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat |
| title_fullStr |
Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat |
| title_full_unstemmed |
Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat |
| title_sort |
modulation of ach release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat |
| url |
http://hdl.handle.net/20.500.12110/paper_0953816X_v17_n1_p119_Santafe |
| work_keys_str_mv |
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