Furosemide alters nonlinear capacitance in isolated outer hair cells.
The outer hair cell (OHC) from the organ of Corti plays a crucial role in hearing through its unique voltage-dependent mechanical responses. Furosemide, one of the loop diuretics, disrupts normal cochlear function. Here we report on direct effects of furosemide on OHC motility-related, voltage-dependent capacitance using the whole-cell patch-clamp technique. Extracellularly applied furosemide reversibly shifted the voltage at peak capacitance (V(pkC(m))) to positive levels. The shift, whose maximum approached 90 mV, evidenced a Hill coefficient of 1.5 and K(1/2) of 10 mM. Changes in the magnitude of nonlinear capacitance were not fully reversible. While it is clear that the overwhelming effect of furosemide on hearing results via its effects on the endolymphatic potential, the present results indicate that furosemide directly alters OHC motility and may, in part, contribute to sensory dysfunction.
Santos-Sacchi
J
J
Section of Otolaryngology, Department of Surgery (Otolaryngology), BML 244, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06510, USA. joseph.santos-sacchi@yale.edu
Wu
M
M
Kakehata
S
S
D000818:Animals; D004232:Diuretics / Q000633:toxicity*; D025802:Electric Capacitance; D005246:Feedback; D005665:Furosemide / Q000633:toxicity*; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology*; D066298:In Vitro Techniques; D009068:Movement / Q000187:drug effects; D018408:Patch-Clamp Techniques
D004232:Diuretics; D005665:Furosemide