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Acute gentamicin ototoxicity in cochlear outer hair cells of the guinea pig
A Ernst1, G Reuter, U Zimmermann
1Department of Otolaryngology, University of Tübingen, Germany.
Abstract:
The acute effects of the aminoglycoside antibiotics gentamicin on isolated cochlear outer hair cells (OHC) was investigated by whole-cell patch-clamp and measurements of the intracellular potassium level by means of the potassium-sensitive dye PBFI. In addition, the accompanying length changes of OHC are described. It could be shown that gentamicin at different concentrations reversibly induces a hyperpolarization by about 5-10 mV, potassium outflow from the cytoplasm (by about 22 mM) and a cellular elongation (by about 10%). It is suggested that these effects are the result of an interaction between gentamicin and the cochlear transduction channels in OHC as suggested earlier. These acute effects are distinctly different from the chronic gentamicin effects which are based on the metabolization of the antibiotics to cause the death of the OHC by interaction with the phosphoinositide signalling cascade.
Insights
Gentamicin causes acute, reversible changes in outer hair cells (OHC), including hyperpolarization and elongation. These effects differ from chronic toxicity, suggesting a distinct mechanism of action.
Area of Science:
- Ototoxicology
- Cell Physiology
- Pharmacology
Background:
- Aminoglycoside antibiotics like gentamicin can cause hearing loss.
- Outer hair cells (OHC) are crucial for hearing sensitivity.
- The acute cellular mechanisms of gentamicin toxicity are not fully understood.
Purpose of the Study:
- To investigate the acute effects of gentamicin on isolated OHC.
- To elucidate the cellular mechanisms underlying gentamicin's ototoxicity.
- To differentiate acute from chronic gentamicin effects on OHC.
Main Methods:
- Whole-cell patch-clamp electrophysiology on isolated OHC.
- Measurement of intracellular potassium levels using PBFI dye.
- Assessment of OHC cellular length changes.
Main Results:
- Gentamicin induced a reversible hyperpolarization of OHC (5-10 mV).
- A significant potassium outflow from OHC cytoplasm was observed (approx. 22 mM).
- Gentamicin caused reversible cellular elongation of OHC (approx. 10%).
Conclusions:
- Acute gentamicin exposure reversibly alters OHC membrane potential, potassium homeostasis, and cell length.
- These effects are likely mediated by gentamicin's interaction with cochlear transduction channels in OHC.
- Acute effects contrast with chronic toxicity, which involves metabolization and OHC death via phosphoinositide signaling.