Protein kinase C involvement in the acetylcholine release reduction induced by amyloid-beta(25-35) aggregates on neuromuscular synapses.
Using intracellular recording of the diaphragm muscle of adult rats, we have investigated the short-term functional effects of amyloid-beta (Abeta(25-35) peptide aggregates on the modulation of acetylcholine (ACh) release and the involvement of protein kinase C (PKC). The non-aggregated form of this peptide does not change the evoked and spontaneous transmitter release parameters on the neuromuscular synapse. However, the aggregated form of Abeta(25-35) acutely interferes with evoked quantal ACh release (approximately 40% reduction) when synaptic activity in the ex vivo neuromuscular preparation is maintained by low frequency (1 Hz) electrical stimulation. This effect is partially dependent on the activity of PKC that may have a permissive action. The end result of Abeta(25-35) is in opposition to the PKC-dependent maintenance effect on ACh release manifested in active synapses.
Tomàs
Marta
M
Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, 43201 Reus, Spain.
Garcia
Neus
N
Santafé
Manuel M
MM
Lanuza
Maria
M
Tomàs
Josep
J
D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000201:enzymology; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D003964:Diaphragm / Q000294:innervation; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009469:Neuromuscular Junction / Q000201:enzymology; D010446:Peptide Fragments / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000201:enzymology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D011493:Protein Kinase C; D000109:Acetylcholine