Acid-Sensitive Ion Channel (Asic) Expression And Function In Chemoafferent Petrosal Ganglion (Pg) Neurons Following Chronic Hypoxia

The current study examines the hypothesis that ASICs are involved in chronic hypoxia (CH, 3–14 days @ BP = 380 Torr)-induced hypersensitivity in rat carotid body. Expression of ASIC1a/1b, ASIC2a and ASIC3 genes were significantly elevated (~1.3–2.5-fold) in the PG following 3 or 7 days of CH. Western immunoblot showed increased expression of ASIC3 protein in PG, but not in nodose ganglion (NG) following CH. Exposure to pH 6.0 solution elicited a moderate increase in [Ca2+] in primary cultures of normal PG neurons. However, following 5–6 daysI of CH, exposure to low pH evoked a significantly enhanced [Ca2+]I-response in many small diameter neurons. The ASICs antagoinist, ibuprofen (200 μM), which has been shown to directly block currents mediated by ASIC3 and ASIC3/2b hetero-multimers, marginally reduced chemoreceptor nerve activity evoked by acute hypoxia in superfused carotid body preparations from normal animals. However following 8–10 days of CH, ibuprofen markedly inhibited evoked nerve activity. Finally, concurrent treatment with ibuprofen (4 mg/kg/day), an agent known to depress ASICs expression associated with chronic inflammation, prevented the CH-induced enhancement of chemosensitivity. The data suggest that low pH and acid metabolites may contribute to depolarization of carotid body afferent terminals in CH adapted animals. USPHS Grants NS 12636 and NS 07938.