, 2000) Resolving the exact value may require determining the pr

, 2000). Resolving the exact value may require determining the prestin half-activation voltage in vivo. In contrast, the predicted IHC resting potential of −55 mV is near the membrane potential at which the voltage-dependent Ca2+ current mediating synaptic transmission begins to activate at

body temperature (−60 mV; Grant and Fuchs, 2008 and Johnson and Marcotti, 2008). The main consequence of a depolarized resting potential in OHCs is full activation of the voltage-dependent K+ conductance, thus minimizing τm and expanding the membrane filter so there is little attenuation of CF receptor potentials. Previous estimates of OHC τm translate into equivalent corner selleck chemicals frequencies an order of magnitude less than the CF (Mammano and Ashmore, 1996, Preyer et al., 1994 and Preyer et al., 1996). For example, corner frequencies of 15, 50, and 480 Hz were measured in turns 4 (CF = 0.5 kHz), 3 (CF = 2 kHz), and 2 (CF = 7 kHz) of the guinea pig cochlea (Mammano and Ashmore, 1996), but this is unsurprising, as the OHCs

had resting potentials of −70 mV where the K+ conductance would be only partially activated. For turns 3 and 4, these lower corner frequencies are similar to the ones measured here when the MT channels of apical gerbil OHCs (CF = 0.35 kHz) were blocked with DHS (about 40 Hz; Figure 4C). Our results demonstrate a similarity between the membrane corner frequency and CF (Figure 7), and if this extends to even higher frequencies, the amplitude of CF receptor potentials will be not greatly attenuated over the entire auditory range. This property removes a major criticism for Selleck PARP inhibitor the contribution of prestin-induced somatic contractility to the cochlear amplifier. To examine the extension to the highest frequencies, the tonotopic gradients were

extrapolated to the upper frequency limit in the rat (55 kHz), giving 700 nS and 130 nS for the K+ and MT conductances, respectively (Figure S1). Using these values and a membrane capacitance of 4.5 pF, a resting potential of −53 mV and a corner frequency of 18 kHz were inferred. As noted earlier, the imperfect agreement between the CF and corner frequency may in part stem from the MT current being underestimated in our experiments. Nevertheless, the approximate match over much of the frequency (-)-p-Bromotetramisole Oxalate range ensures activation of prestin by receptor potentials at CF facilitating its role in cochlear amplification. More work is needed to determine whether other mechanisms, such as extracellular potential fields (Mistrík et al., 2009), also contribute at the highest CFs. Recordings were made from OHCs in isolated organs of Corti of Sprague-Dawley rats and Mongolian gerbils between 6 and 28 days postnatal (P6–P28, where P0 is the birth date) and IHCs from gerbils (P8 and P18) using methods previously described (Kennedy et al., 2003, Marcotti et al., 2005 and Johnson and Marcotti, 2008).

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