Joseph Santos-Sacchi

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Myosin VIIa is a newly identified member of the myosin superfamily of actin-based motors. Recently, the myosin VIIa gene was identified as the gene defective in shaker-1, a recessive deafness in mice [Gibson, F., Walsh, J., Mburu, P., Varela, A., Brown, K.A., Antonio, M., Beisel, K.W., Steel, K.P. & Brown, S.D.M. (1995) Nature (London) 374, 62-64], and in(More)
The unique electromotility of the outer hair cell (OHC) is believed to promote sharpening of the passive mechanical vibration of the mammalian basilar membrane. The cell also presents a voltage-dependent capacitance, or equivalently, a nonlinear gating current, which correlates well with its mechanical activity, suggesting that membrane-bound voltage(More)
The outer hair cell lateral membrane motor, prestin, drives the cell's mechanical response that underpins mammalian cochlear amplification. Little is known about the protein's structure-function relations. Here we provide evidence that prestin is a 10-transmembrane domain protein whose membrane topology differs from that of previous models. We also present(More)
Salicylate, one of the most widely used drugs, is known to induce reversible tinnitus and hearing loss. Salicylate interferes with outer hair cells (OHCs), which are believed to underlie normal auditory frequency selectivity and sensitivity. In the present experiments, the effects of salicylate and lanthanides on OHC motility and nonlinear capacitance were(More)
The outer hair cell (OHC) possesses a nonlinear charge movement whose characteristics indicate that it represents the voltage sensor responsible for OHC mechanical activity. OHC mechanical activity is known to exist along a restricted extent of the cell's length. We have used a simultaneous partitioning microchamber and whole cell voltage clamp technique to(More)
1. Isolated outer hair cells (OHCs) from the guinea-pig were whole-cell voltage clamped to study the influence of initial voltage on the voltage dependence of motility-related gating current or, equivalently, on the voltage dependence of membrane capacitance. 2. Prepulse delivery caused changes in the magnitude of motility-related gating currents, which are(More)
Whole cell voltage clamp and freeze fracture were used to study the electrophysiological and ultrastructural correlates of the outer hair cell (OHC) lateral membrane molecular motors. We find that specific voltage-dependent capacitance, which derives from motility-related charge movement, increases as cell length decreases. This increasing non-linear charge(More)
Whole-cell voltage clamp and displacement-measuring photodiode techniques were used to study electrophysiological and mechanical properties of the guinea pig outer hair cell (OHC). OHCs demonstrate a voltage-mechanical response (V-M) function that can be fit by a two state Boltzmann relation, where the cell normally rests near the hyperpolarizing saturation(More)
Type I spiral ganglion cells provide the afferent innervation to the inner hair cells of the mammalian organ of Corti and project centrally to the cochlear nucleus. While single-unit studies conducted over the past several decades have provided a wealth of information concerning the response characteristics of these neurons and, to some extent, their(More)
The outer hair cell (OHC) from the organ of Corti is believed to be responsible for the mammal's exquisite sense of hearing. A membrane-based motile response of this cell underlies the initial processing of acoustic energy. The voltage-dependent capacitance of the OHC, possibly reflecting charge movement of the motility voltage sensor, was measured in cells(More)