Aminoglycosides block the Kv3.1 potassium channel and reduce the ability of inferior colliculus neurons to fire at high frequencies.
The Kv3.1 potassium channel is expressed at high levels in auditory nuclei and contributes to the ability of auditory neurons to fire at high frequencies. We have tested the effects of streptomycin, an agent that produces progressive hearing loss, on the firing properties of inferior colliculus neurons and on Kv3.1 currents in transfected cells. We found that in inferior colliculus neurons, intracellular streptomycin decreased the current density of a high threshold, noninactivating outward current and reduced the rate of repolarization of action potentials and the ability of these neurons to fire at high frequencies. Furthermore, potassium current in CHO cells transfected with the Kv3.1 gene was reduced by 50% when cells were cultured in the presence of streptomycin or when streptomycin was introduced intracellularly in the pipette solution. In the presence of intracellular streptomycin, the activation rate of Kv3.1 current increased and inhibition by extracellular TEA become voltage-dependent. The data indicate that streptomycin inhibits Kv3.1 currents by inducing a conformational change in the Kv3.1 channel. The hearing loss caused by aminoglycoside antibiotics may be partially mediated by their inhibition of Kv3.1 current in auditory neurons.
Liu
Si-Qiong J
SQ
Department of Biology, Penn State University, 419 Mueller Lab, State College, Pennsylvania 16802, USA. sjl16@psu.edu
Kaczmarek
Leonard K
LK
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000617:Aminoglycosides / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D066298:In Vitro Techniques; D007245:Inferior Colliculi / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000037:antagonists & inhibitors* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051670:Shaw Potassium Channels; D013307:Streptomycin / Q000494:pharmacology
D000617:Aminoglycosides; D009479:Neuropeptides; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D051670:Shaw Potassium Channels; D013307:Streptomycin