Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na+ channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca2+ and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor-dependent long-term depression (LTD) in the hippocampus. We found that ASIC1a channels mediate a component of LTD in P30-40 animals, since the ASIC1a selective blocker psalmotoxin-1 (PcTx1) reduced the magnitude of LTD induced by application of the group I mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) or induced by paired-pulse low frequency stimulation (PP-LFS). Conversely, PcTx1 did not affect LTD in P13-18 animals. We also provide evidence that ASIC1a is involved in group I mGlu receptor-induced increase in action potential firing. However, blockade of ASIC1a did not affect DHPG-induced polyphosphoinositide hydrolysis, suggesting the involvement of some other molecular partners in the functional crosstalk between ASIC1a and group I mGlu receptors. Notably, PcTx1 was able to prevent the increase in GluA1 S845 phosphorylation at the post-synaptic membrane induced by group I mGlu receptor activation. These findings suggest a novel function of ASIC1a channels in the regulation of group I mGlu receptor synaptic plasticity and intrinsic excitability.

Mango, D., Braksator, E., Battaglia, G., Marcelli, S., Mercuri, N.b., Feligioni, M., et al. (2017). Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus. PHARMACOLOGICAL RESEARCH, 119, 12-19 [10.1016/j.phrs.2017.01.028].

Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus

Mango, D;MERCURI, NICOLA BIAGIO;NISTICO', ROBERT GIOVANNI
2017-01-01

Abstract

Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na+ channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca2+ and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor-dependent long-term depression (LTD) in the hippocampus. We found that ASIC1a channels mediate a component of LTD in P30-40 animals, since the ASIC1a selective blocker psalmotoxin-1 (PcTx1) reduced the magnitude of LTD induced by application of the group I mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) or induced by paired-pulse low frequency stimulation (PP-LFS). Conversely, PcTx1 did not affect LTD in P13-18 animals. We also provide evidence that ASIC1a is involved in group I mGlu receptor-induced increase in action potential firing. However, blockade of ASIC1a did not affect DHPG-induced polyphosphoinositide hydrolysis, suggesting the involvement of some other molecular partners in the functional crosstalk between ASIC1a and group I mGlu receptors. Notably, PcTx1 was able to prevent the increase in GluA1 S845 phosphorylation at the post-synaptic membrane induced by group I mGlu receptor activation. These findings suggest a novel function of ASIC1a channels in the regulation of group I mGlu receptor synaptic plasticity and intrinsic excitability.
2017
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
ASIC; Electrophysiology; Hippocampus; LTD; mGlu receptors;
Mango, D., Braksator, E., Battaglia, G., Marcelli, S., Mercuri, N.b., Feligioni, M., et al. (2017). Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus. PHARMACOLOGICAL RESEARCH, 119, 12-19 [10.1016/j.phrs.2017.01.028].
Mango, D; Braksator, E; Battaglia, G; Marcelli, S; Mercuri, Nb; Feligioni, M; Nicoletti, F; Bashir, Z; Nistico', Rg
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/185712
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