IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
artículos
Título:
Acid Sensing Ion Channels 1a (Asic-1a) Inhibit neuromuscular Transmission In Female Mice.
Autor/es:
# URBANO FJ & # LINO NG CONTRIBUTED EQUALLY AS FIRST AUTHORS; #LINO NG; GONZALEZ INCHAUSPE C; GONZALES LE; COLETTIS N; VATTINO LG; WUNSCH AM; WEMMIE J; UCHITEL OD
Revista:
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Editorial:
AMER PHYSIOLOGICAL SOC
Referencias:
Lugar: Bethesda; Año: 2014 vol. 306 p. 396 - 406
ISSN:
0363-6143
Resumen:
Urbano FJ & Lino NG contributed equally as first authors. Urbano FJ was the corresponding author of this work.----------------------------------- Acid-sensing ion channels (ASIC) open in response to extracellular acidosis. ASIC1a, a particular subtype of these channels, have been described to have a post-synaptic distribution in the brain, being involved not only in ischemia and epilepsy, but also in fear and psychiatric pathologies. High frequency stimulation of skeletal motor nerve terminals (MNTs) can induce presynaptic pH changes in combination with an acidification of the synaptic cleft, known to contribute to muscle fatigue. Here, we studied the role of ASIC1a channels on neuromuscular transmission. We combined behavioral wire hanging test with electrophysiology, pharmacological and immunofluorescence techniques to compare wildtype and ASIC1a lacking mice (ASIC1a -/- knockout). Our results showed: 1) ASIC1a -/- female mice were weaker than wildtype, presenting shorter times during the wire hanging test. 2) Spontaneous neurotransmitter release were reduced by ASIC1a activation, suggesting a presynaptic location of these channels at individual MNTs. 3) ASIC-1a-mediated effects were emulated by extracellular local application of acid saline solutions (pH=6.0; Hepes+MES-based solution). 4) Immunofluorescence techniques revealed the presence of ASIC1a antigens on MNTs. These results suggest that ASIC1a channels might be involved in controlling neuromuscular transmission, muscle contraction and fatigue in female mice.