title: Calcium inflow-dependent protein kinase C activity is involved in the modulation of transmitter release in the neuromuscular junction of the adult rat.
abstract: Using intracellular recording, we studied how protein kinase C activity affected miniature endplate potentials (MEPPs) and evoked endplate potentials (EPPs) in the neuromuscular junctions of the levator auris longus muscle from adult rats. The protein kinase C activator phorbol 12-myristate 13-acetate (PMA, 10 nM) increased the quantal content by approximately 150% (P<0.05). On the other hand, the quantal content decreased by approximately 40% (P<0.05) for all the protein kinase C inhibitors tested (Calphostin-C, 10 microM; Chelerythrine, 1 microM; Staurosporine, 200 nM). These changes in acetylcholine release were maintained at plateau for 1 to 7 h. Moreover, none of the protein kinase C activators or inhibitors used could modify the spontaneous MEPP mean size (P>0.05). We reduced the calcium influx in nerve terminals using the P/Q-type channel blocker omega-Aga-IVA(100 nM) or with 5 mM magnesium in physiological solution. In neither situation was the quantal content modified by PMA or by CaC. However, when high Ca2+ (5 mM) was added to a preparation that was previously blocked with omega-Aga-IVA, PMA and CaC had their full effect. We conclude that under physiological conditions PKC is dependent on the calcium inflow through the P/Q-type voltage-dependent calcium channels during evoked activity and works near the maximum rate at normal external calcium concentration.
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, 43201-Reus, Spain. msm@fmcs.urv.es
authors.forename: M M
authors.initials: MM
authors.lastname: Santafé
authors.forename: M A
authors.initials: MA
authors.lastname: Lanuza
authors.forename: N
authors.initials: N
authors.lastname: Garcia
authors.forename: J
authors.initials: J
authors.lastname: Tomàs
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002273:Carcinogens / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020865:Calcium Channels, P-Type; D002273:Carcinogens; D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium