Acid-Sensing Ionic Channels in the Rat Vestibular Endorgans and Ganglia

• Published in: Journal of neurophysiology 2006-09, Vol.96 (3), p.1615-1624
• Main Authors: Mercado, Francisco, Lopez, Ivan A, Acuna, Dora, Vega, Rosario, Soto, Enrique
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Afferent Pathways - physiology; Animals; Cell Membrane - physiology; Ganglia - physiology; Hair Cells, Auditory - physiology; Hydrogen-Ion Concentration; Ion Channels - physiology; Male; Membrane Potentials - physiology; Patch-Clamp Techniques; Protons; Rats; Rats, Sprague-Dawley; Rats, Wistar; Vestibule, Labyrinth - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00378.2006

1 Instituto de Fisiología, Universidad Autónoma de Puebla, Puebla; 2 Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Distrito Federal, Mexico City, Mexico; and 3 Surgery Department (Division of Head and Neck) and 4 Mental Retardation Research Center, David Geffen School of Medicine at University of California, Los Angeles, California Submitted 10 April 2006; accepted in final form 7 June 2006 Acid-sensing ionic channels (ASICs) are members of the epithelial Na + channel/degenerin (ENaC/DEG) superfamily. ASICs are widely distributed in the central and peripheral nervous system. They have been implicated in synaptic transmission, pain perception, and the mechanoreception in peripheral tissues. Our objective was to characterize proton-gated currents mediated by ASICs and to determine their immunolocation in the rat vestibular periphery. Voltage clamp of cultured afferent neurons from P7 to P10 rats showed a proton-gated current with rapid activation and complete desensitization, which was carried almost exclusively by sodium ions. The current response to protons (H + ) has a pH 0.5 of 6.2. This current was reversibly decreased by amiloride, gadolinium, lead, acetylsalicylic acid, and enhanced by FMRFamide and zinc, and negatively modulated by raising the extracellular calcium concentration. Functional expression of the current was correlated with smaller-capacitance neurons. Acidification of the extracellular pH generated action potentials in vestibular neurons, suggesting a functional role of ASICs in their excitability. Immunoreactivity to ASIC1a and ASIC2a subunits was found in small vestibular ganglion neurons and afferent fibers that run throughout the macula utricle and crista stroma. ASIC2b, ASIC3, and ASIC4 were expressed to a lesser degree in vestibular ganglion neurons. The ASIC1b subunit was not detected in the vestibular endorgans. No acid-pH–sensitive currents or ASIC immunoreactivity was found in hair cells. Our results indicate that proton-gated current is carried through ASICs and that ionic current activated by H + contributes to shape the vestibular afferent neurons' response to its synaptic input. Address for reprint requests and other correspondence: F. Mercado, Instituto de Fisiología–BUAP, Apartado Postal 406, Puebla, Pue. 72000, Mexico (E-mail: chimera{at}puebla.megared.net.mx )