title: The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction.
abstract: BACKGROUND
  Various protein kinase C (PKC) isoforms contribute to the phosphorylating activity that modulates neurotransmitter release. In previous studies we showed that nPKCε is confined in the presynaptic site of the neuromuscular junction and its presynaptic function is activity-dependent. Furthermore, nPKCε regulates phorbol ester-induced acetylcholine release potentiation, which further indicates that nPKCε is involved in neurotransmission. The present study is designed to examine the nPKCε involvement in transmitter release at the neuromuscular junction.
  
  
  RESULTS
  We use the specific nPKCε translocation inhibitor peptide εV1-2 and electrophysiological experiments to investigate the involvement of this isoform in acetylcholine release. We observed that nPKCε membrane translocation is key to the synaptic potentiation of NMJ, being involved in several conditions that upregulate PKC isoforms coupling to acetylcholine (ACh) release (incubation with high Ca(2+), stimulation with phorbol esters and protein kinase A, stimulation with adenosine 3',5'-cyclic monophosphorothioate, 8-Bromo-, Rp-isomer, sodium salt -Sp-8-BrcAMP-). In all these conditions, preincubation with the nPKCε translocation inhibitor peptide (εV1-2) impairs PKC coupling to acetylcholine release potentiation. In addition, the inhibition of nPKCε translocation and therefore its activity impedes that presynaptic muscarinic autoreceptors and adenosine autoreceptors modulate transmitter secretion.
  
  
  CONCLUSIONS
  Together, these results point to the importance of nPKCε isoform in the control of acetylcholine release in the neuromuscular junction.
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Obis
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain.
authors.forename: Erica
authors.initials: E
authors.lastname: Hurtado
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Nadal
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Tomàs
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Priego
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Simon
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Garcia
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain.
authors.forename: Manel M
authors.initials: MM
authors.lastname: Santafe
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain. mariaangel.lanuza@urv.cat.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lanuza
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Sant Llorenç 21, 43201, Reus, Spain. josepmaria.tomas@urv.cat.
authors.forename: Josep
authors.initials: J
authors.lastname: Tomàs
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000201:enzymology*; D010455:Peptides / Q000494:pharmacology; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D010455:Peptides; D011976:Receptors, Muscarinic; D011983:Receptors, Purinergic; D018047:Receptors, Purinergic P1; D017868:Cyclic AMP-Dependent Protein Kinases; D051744:Protein Kinase C-epsilon; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium