ABSTRACT
OBJECTIVE: This study evaluated the ability of dihydrostreptomycin (DHSM) to go through the mechano-electric transduction (MET) channels in hair cells under physiological conditions. MATERIALS AND METHODS: Tall hair cells were isolated from the chick basilar membrane (cochlea). Mechanical stimulation was applied by a glass rod attached to a piezoelectric bimorph, and MET currents were recorded with a whole-cell patch technique. The voltage-dependent block of DHSM to MET channel was estimated by calculating the relative conductances (the ratio of MET current in DHSM saline to DHSM-free saline) at various membrane potentials. RESULTS AND CONCLUSION: At membrane potentials between -100 and +50 mV, DHSM behaves as a voltage-dependent blocker according to a partial block model. At membrane potentials more negative than -100 mV, however, DHSM blocking decreased. This finding differed from the partial block model, but indicated that DHSM escaped through the channel pore into the cytoplasm by acting as a permeant channel blocker due to the large electrical driving force.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Dihydrostreptomycin Sulfate/pharmacokinetics , Hair Cells, Auditory/drug effects , Ion Channel Gating/drug effects , Ion Channels/antagonists & inhibitors , Animals , Chickens , Cytoplasm/metabolism , Hair Cells, Auditory/physiology , In Vitro Techniques , Ion Channels/physiology , Mechanotransduction, Cellular/physiology , Membrane Potentials/drug effects , Membrane Potentials/physiology , Models, Biological , Patch-Clamp TechniquesABSTRACT
Tetraethylammonium (TEA)-sensitive potassium currents in the cochlear inner hair cells (IHCs) possess the kinetics of fast inactivation. IHCs of guinea-pigs were separately isolated from the apical and basal turns and the tonotopic gradient of inactivation kinetics was investigated. TEA-sensitive potassium currents showed voltage-dependent time constant of the inactivation phase both in apical and basal IHCs, however, the degree of inactivation (compared to the ratio between the steady-state current and initial peak current) was voltage-independent. Inactivation time constant was faster in basal IHCs than in apical IHCs and the degree of inactivation was greater in basal IHCs than in apical IHCs, suggesting that inactivation was more predominant in basal IHCs than in apical IHCs.
