46 ± 0.08, n = 6) was similar to that obtained with K+. This indicates that the perfusion of the endolymph-like K+ solution was restricted to the hair bundles. In either case the consequence was a large standing MT current in low Ca2+ and in the absence of stimulation. The C59 wnt manufacturer presence of this standing inward current in the endolymph solution (0.94 ± 0.04 nA), which may be termed a “silent current” by analogy with the dark current in photoreceptors (Baylor et al., 1979), meant that OHCs exhibited a significantly more depolarized

membrane potential (−34 ± 3 mV, n = 7: p < 0.002) compared to that in perilymph (−51 ± 2 mV, n = 5). Because the MT current in OHCs has a reversal potential near 0 mV (Kros et al., 1992 and Beurg et al., 2006), ISRIB nmr only a small electrical driving force exists in isolated preparations that lack the 90 mV endolymphatic potential. Nevertheless, substantial receptor potentials of 40–60 mV could be measured under current clamp conditions (Figures 1C and 1D). The mean receptor potential for a saturating stimulus was 51 ± 8 mV (n = 5) in perilymph and 42 ± 2 mV (n = 7) in endolymph. These responses were obtained for 0.1–0.2 μm

maximum hair bundle displacements giving current-displacement relations that could be fit by a single Boltzmann (Figures 1E and 1F). Similar effects on the transduction current and receptor potential were also seen in OHCs of the isolated gerbil cochlea on exposing the hair bundles to endolymphatic Ca2+. MT currents measured at room temperature in the gerbil apex (CF = 0.35 kHz) increased from 0.67 ± 0.01 nA in normal 1.3 mM Ca2+ (n = 5) to 1.19 ± 0.05 nA

in endolymph 0.02 mM Ca2+ (n = 7) and the fraction of current activated at rest increased under the same circumstance from 0.08 ± 0.01 to 0.43 ± 0.04. The increase in standing current in low Ca2+ was not attributable to activation of other conductances because it was fully abolished (Figures 2A and 2B) by addition of 0.2 mM dihydrostreptomycin Sodium butyrate (DHS), a known blocker of the OHC MT channel. In both gerbils and rats, the size of the MT current increased systematically with the CF of the OHC. Measurements were made at multiple cochlear locations, the CFs of which were interpolated from existing frequency maps for the two rodents (Müller, 1991 and Müller, 1996). The two animal species were chosen because they have different but overlapping frequency ranges, the gerbil from 0.2–35 kHz and the rat from 1–55 kHz. Examples of MT currents in low Ca2+ for the gerbil are shown in Figures 2A and 2B. In the presence of 0.02 Ca2+ and either Na+ or K+, apical-coil gerbil OHCs (0.9 kHz) exhibited a similar MT current (Na+: 1.56 ± 0.25 nA, n = 5; K+: 1.52 ± 0.16 nA, n = 5) and MT channel resting open probability (Na+: 0.46 ± 0.01, n = 5; K+: 0.45 ± 0.05 nA, n = 5), confirming that the effects seen in the presence of the endolymph-like solution are only due to the low Ca2+ concentration.