MECHANOTRANSDUCTION IN COCHLEAR OUTER HAIR CELLS

Anthony W. Gummer University of Tübingen, Dept. Otolaryngology, Germany

Cochlear outer hair cells are responsible for the exquisite sensitivity, frequency selectivity and dynamic range of the cochlea. Deflection of their stereocilia results in modulation of the open probability of mechanosensitive ion channels located near the tips of the stereocilia. The resulting current causes a change of the membrane potential, which in turn produces mechanical force that is fed back into the organ of Corti. The transducer channels in the stereocilia have long been proposed to be gated directly by tension in the tip links. These are thin, elastic extracellular elements connecting the tips of adjacent stereocilia. If this hypothesis is true, the channels should close after destruction of the tip links. To test this hypothesis, the tip links of outer hair cells isolated from the guinea-pig cochlea were destroyed, either enzymatically (elastase, 20 U/mL) or non-enzymatically (BAPTA, 5 mM), and the time course of the receptor current measured in whole-cell voltage-clamp. Contrary to the hypothesis, loss of tip links resulted not in a loss of current but in a tonic current with similar amplitude to that of the control receptor current. The tonic current exhibited similar pharmacological properties (100-µM DHSM, 300-µM amiloride, or 1-mM Gd³⁺) to the receptor current. The tonic current could be modulated exponentially by “static“ deflection of the stereocilia; the time constant was 1-2 sec. The time constant was reduced by increasing the intracellular calcium concentration (25-µM NP-EGTA/AM, 10-µM CG-1/AM). These experiments imply an intracellular, calcium-dependent gating mechanism for hair-cell mechanotransducer channels, that is independent of the presence of tip links.