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Published on: October 17, 2012
Furosemide alters nonlinear capacitance in isolated outer hair cells
J Santos-Sacchi1, M Wu, S Kakehata
1Section 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
Furosemide, a loop diuretic, directly impacts outer hair cell (OHC) function by altering voltage-dependent capacitance, potentially contributing to hearing dysfunction beyond its known effects on cochlear potential.
Area of Science:
- Oto-neuroscience
- Pharmacology
- Cell Physiology
Background:
- Outer hair cells (OHCs) in the organ of Corti are vital for hearing due to their voltage-dependent mechanical responses.
- Furosemide, a loop diuretic, is known to disrupt cochlear function.
Purpose of the Study:
- To investigate the direct effects of furosemide on the voltage-dependent capacitance of OHCs, which is related to their motility.
- To elucidate the direct cellular mechanisms by which furosemide may affect hearing.
Main Methods:
- Whole-cell patch-clamp technique was employed to measure voltage-dependent capacitance in OHCs.
- Extracellular application of furosemide was used to observe its effects on OHC capacitance.
Main Results:
- Extracellular furosemide caused a reversible, positive shift in the voltage at peak capacitance (V(pkC(m))), with a maximum shift of approximately 90 mV.
- The furosemide-induced shift exhibited a Hill coefficient of 1.5 and a K(1/2) of 10 mM.
- Observed changes in nonlinear capacitance magnitude were not entirely reversible.
Conclusions:
- Furosemide directly alters OHC motility by affecting their voltage-dependent capacitance.
- While furosemide's primary impact on hearing is through the endolymphatic potential, these direct OHC effects may also contribute to auditory sensory dysfunction.
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