IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ACID SENSING ION CHANNELS 1a (ASIC1a) INHIBIT NEUROMUSCULAR TRANSMISSION IN MICE: A NOVEL MECHANISM OF PRESYNAPTIC CONTROL
Autor/es:
FRANCISCO J. URBANO, CARLOTA M. GONZÁLEZ-INCHAUSPE, LAURA E. GONZALEZ, MARÍA E. LÓPEZ, AMANDA M. WUNSCH, JOHN A. WEMMIE & OSVALDO D. UCHITEL
Lugar:
University of New England, Maine, USA
Reunión:
Conferencia; Gordon Research Conferences; 2010
Institución organizadora:
Gordon Research Conferences
Resumen:
We studied the possible role of acid sensing ion channel 1a (ASIC1a) at the neuromuscular junction. We found that ASIC1a-polyclonal antibodies preferentially labeled the neuromuscular junction of levator auris muscles from wildtype mice compared to ASIC1a-/- mice. ASIC1a-specific immmunofluoresence co-localized better with the presynaptic marker synaptophysin than with the postsynaptic marker  rhodamine-conjugated- -bungarotoxin, suggesting a presynaptic pattern of distribution. Consistent with these findings, disrupting ASIC1a or inhibiting it with psalmotoxin increased the frequency of spontaneous miniature endplate potentials (MEPPs).             Furthermore, lowering extracellular pH to 6.0 reduced the frequency of MEPPs and significantly  increased paired-pulse ratios of end plate potententials (EPPs) in wildtype mice but not in ASIC1a-/- mice.             Disrupting ASIC1a or inhibiting it with psalmotoxin also significantly increased EPP facilitation  during trains of repetitive stimulation (75 Hz, 5 sec).             Finally, we observed ASIC1a-mediated inhibition of FM2-10-labeled vesicle turnover.             Together these results suggest that ASIC1a is present at the neuromuscular junction of adult mice, that ASIC1a negatively controls acetylcholine (ACh) release during both low and high frequency stimulation, and that the effects are sensitive to changes in extracellular pH. Such novel mechanism might help understand how neuromuscular transmitter release can be protected from drastic skeletal muscle lactic acidosis.