Tetanic failure due to decreased endogenous adenosine A(2A) tonus operating neuronal Ca(v)1 (L-type) influx in Myasthenia gravis

• Tipo: Artigo em Revista Científica Internacional
• Data: 2011

Autores

Noronha Matos, JB (Autor) ICBAS; Morais, T (Autor) Outra; Trigo, D (Autor) Outra; Timoteo, MA (Autor) Outra; Magalhaes Cardoso, MT (Autor) Outra; oliveira, l (Autor) ICBAS; Paulo Correia de Sá (Autor) ICBAS

Revista

Título: Journal of Neurochemistry

Vol. 117

Páginas: 797-811

ISSN: 0022-3042

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 29 Citações

Scopus - 30 Citações

Outras Informações

ID Authenticus: P-002-R90

DOI: 10.1111/j.1471-4159.2011.07216.x

Abstract (EN): P>In healthy motor endplates, tetanic depression is overcome by tonic adenosine A(2A)-receptor-mediated facilitation of transmitter release. The A(2A) receptor operates a coordinated shift from fast-desensitizing Ca(v)2.1 (P/Q) calcium influx to long-lasting Ca(V)1 (L) channels on motor nerve terminals. This study aimed at investigating whether A(2A) receptors-operated Ca2+ influx via Ca(V)1 (L)-type channels contribute to sustain acetylcholine release evoked by 50 Hz-bursts in toxin-induced Myasthenia gravis (TIMG) rats. In contrast to control animals, inhibition of [3H]acetylcholine (ACh) release by the Ca(V)2.1 (P/Q) channel blocker, omega-Agatoxin IVA (100 nM), in TIMG rats had a higher magnitude than that observed with the Ca(V)1 (L) channel blocker, nifedipine (1 mu M). Adenosine deaminase (0.5 U/mL) and the A(2A) receptor antagonist, ZM 241385 (50 nM), decreased [3H]ACh release by a similar amount in control rats, but their effects were smaller in magnitude in myasthenic animals. The adenosine precursor, AMP (100 mu M), increased (similar to 40%) ACh release in both control and TIMG animals. Blockade of A(2A), but not of A(1), receptors prevented AMP-induced facilitation of transmitter release; nifedipine (1 mu M) mimicked the effect of the A(2A) receptor antagonist. Video-microscopy studies designed to measure real-time transmitter exocytosis using the FM4-64 fluorescent dye fully supported radiochemical data. Thus, impairment of the adaptive shift from Ca(V)2.1 (P/Q) to Ca(V)1 (L) channels may contribute to tetanic failure in myasthenic rats. This parallels the reduction of adenosine A(2A) receptor tonus in TIMG animals, which might be restored by exogenous application of AMP.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 15