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• W2085451289 abstract "1. The effects of amiloride and amiloride derivatives on mechano-electrical transducer currents in outer hair cells of the cultured neonatal mouse cochlea were examined under whole-cell voltage clamp. 2. At -84 mV transducer currents were reversibly blocked by the extracellular application of the pyrazinecarboxamides amiloride, benzamil, dimethylamiloride, hexamethyleneiminoamiloride, phenamil and methoxynitroiodobenzamil with half-blocking concentrations of 53, 5.5, 40, 4.3, 12 and 1.8 microM, respectively. Hill coefficients were determined for all but the last of these compounds and were 1.7, 1.6, 1.0, 2.2 and 1.6, respectively, suggesting that two drug molecules co-operatively block the transducer channel. 3. Both the structure-activity sequence for amiloride and its derivatives and the mechanism of the block of the transducer channel appear to be different from those reported for the high-affinity amiloride-sensitive epithelial Na+ channels but similar to those of stretch-activated channels in Xenopus oocytes. 4. The block by all pyrazinecarboxamides was voltage dependent with positive membrane potentials releasing the block. The form of the voltage dependence is consistent with a voltage-independent binding of the drug to a site that is accessible at hyperpolarized but not at depolarized potentials, suggesting that the transducer channel undergoes a voltage-dependent conformational change. The channel was not blocked by 1 mM amiloride from the intracellular side at either negative or positive membrane potentials. 5. The kinetics of the block were studied using force steps or voltage jumps. The results suggest that the drug binding site is only accessible when the transducer channel is open (open-channel block) and that the channel cannot close when the drug molecules are bound. 6. The time dependence and voltage dependence of the block together reveal that the transducer channel has at least two open conformational states, the transition between which is voltage dependent." @default.
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• W2085451289 date "1994-01-01" @default.
• W2085451289 modified "2023-10-15" @default.
• W2085451289 title "Block by amiloride and its derivatives of mechano-electrical transduction in outer hair cells of mouse cochlear cultures." @default.
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• W2085451289 doi "https://doi.org/10.1113/jphysiol.1994.sp020004" @default.
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