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Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice.

Taylor R, Bullen A, Johnson SL, Grimm-Günter EM, Rivero F, Marcotti W, Forge A, Daudet N - Hum. Mol. Genet. (2014)

Bottom Line: Several actin-associated proteins are essential for stereocilia formation and maintenance, and their absence leads to deafness.Auditory hair cells developed normally in Pls1 KO, but in young adult animals, the stereocilia of inner hair cells were reduced in width and length.These results show that in contrast to other actin-bundling proteins such as espin, harmonin or Eps8, plastin 1 is dispensable for the initial formation of stereocilia.

View Article: PubMed Central - PubMed

Affiliation: Centre for Auditory Research, UCL Ear Institute, University College London, London, UK.

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Mechanotransducer currents in OHCs from Pls1 KO mice. (A, B) Saturating transducer currents recorded from a P5 het (A) and Pls1 KO (B) apical-coil OHC by applying a 50-Hz sinusoidal force stimuli to the hair bundles at the potential of −121 mV and +99 mV. The driver voltage (DV) signal of ±40 V to the fluid jet is shown above the traces (negative deflections of the DV are inhibitory). The arrows indicate the closure of the transducer channels, i.e. disappearance of the resting current, during inhibitory bundle displacements at −121 mV and +99 mV, respectively. Dashed lines indicate the holding current. (C) Peak-to-peak current–voltage curves were obtained from 7 het and 12 Pls1 KO OHCs (P5–P8) using 1.3 mm extracellular Ca2+. The fits through the data are according to Equation 1 (see Material and methods) with values: het k = 418 ± 33, Vr = 1.3 ± 0.3 mV, Vs = 38 ± 2 mV and γ = 0.42 ± 0.01; Pls1 KO k = 418 ± 40, Vr = 1.1 ± 0.4 mV, Vs = 40 ± 3 mV and γ = 0.41 ± 0.01.
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DDU417F8: Mechanotransducer currents in OHCs from Pls1 KO mice. (A, B) Saturating transducer currents recorded from a P5 het (A) and Pls1 KO (B) apical-coil OHC by applying a 50-Hz sinusoidal force stimuli to the hair bundles at the potential of −121 mV and +99 mV. The driver voltage (DV) signal of ±40 V to the fluid jet is shown above the traces (negative deflections of the DV are inhibitory). The arrows indicate the closure of the transducer channels, i.e. disappearance of the resting current, during inhibitory bundle displacements at −121 mV and +99 mV, respectively. Dashed lines indicate the holding current. (C) Peak-to-peak current–voltage curves were obtained from 7 het and 12 Pls1 KO OHCs (P5–P8) using 1.3 mm extracellular Ca2+. The fits through the data are according to Equation 1 (see Material and methods) with values: het k = 418 ± 33, Vr = 1.3 ± 0.3 mV, Vs = 38 ± 2 mV and γ = 0.42 ± 0.01; Pls1 KO k = 418 ± 40, Vr = 1.1 ± 0.4 mV, Vs = 40 ± 3 mV and γ = 0.41 ± 0.01.

Mentions: Besides its role in maintaining the morphology and structure of adult hair cell stereocilia, plastin 1 may be important for mechanoelectrical transduction. To test this, mechanoelectrical transducer (MET) currents were recorded from P5–P8 apical-coil OHCs by displacing their hair bundles in the excitatory and inhibitory direction using a piezo-driven fluid-jet (26,27). The apparent overall steady-state stiffness of the hair bundle measured in het OHCs (6.3 ± 0.6 mN/m, n = 16) was similar to that of Pls1 KO cells (8.3 ± 1.0 mN/m, n = 11) and comparable with that measured from wild-type mouse OHCs in organotypic cultures (28). Upon moving the bundles towards the taller stereocilia (i.e. in the excitatory direction) and at negative membrane potentials, a large inward MET current could be elicited in OHCs from both het and Pls1 KO mice (Fig. 8A and B). The maximum MET current was found to be similar between het (−937 ± 46 pA at −81 mV, n = 7) and KO cells (−843 ± 34 pA at −81 mV, n = 12). Any resting current flowing through open MET channels in the absence of mechanical stimulation was reduced when bundles were moved towards the shorter stereocilia (i.e. in the inhibitory direction) in all het and Pls1 KO OHCs (Fig. 8A and B, arrows). Because the MET current reverses near 0 mV, it became outward when excitatory bundle stimulation was applied during voltage steps positive to its reversal potential (Fig. 8A–C). At positive potentials, the larger resting transducer current (e.g. at +99 mV in Fig. 8A and B: arrows) is due to an increased open probability of the transducer channel resulting from a reduced driving force for Ca2+ influx (29,30). The above-mentioned results indicate that the biophysical properties of the transducer channel, including the presence of a resting current, are not affected by the absence of plastin 1.Figure 8.


Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice.

Taylor R, Bullen A, Johnson SL, Grimm-Günter EM, Rivero F, Marcotti W, Forge A, Daudet N - Hum. Mol. Genet. (2014)

Mechanotransducer currents in OHCs from Pls1 KO mice. (A, B) Saturating transducer currents recorded from a P5 het (A) and Pls1 KO (B) apical-coil OHC by applying a 50-Hz sinusoidal force stimuli to the hair bundles at the potential of −121 mV and +99 mV. The driver voltage (DV) signal of ±40 V to the fluid jet is shown above the traces (negative deflections of the DV are inhibitory). The arrows indicate the closure of the transducer channels, i.e. disappearance of the resting current, during inhibitory bundle displacements at −121 mV and +99 mV, respectively. Dashed lines indicate the holding current. (C) Peak-to-peak current–voltage curves were obtained from 7 het and 12 Pls1 KO OHCs (P5–P8) using 1.3 mm extracellular Ca2+. The fits through the data are according to Equation 1 (see Material and methods) with values: het k = 418 ± 33, Vr = 1.3 ± 0.3 mV, Vs = 38 ± 2 mV and γ = 0.42 ± 0.01; Pls1 KO k = 418 ± 40, Vr = 1.1 ± 0.4 mV, Vs = 40 ± 3 mV and γ = 0.41 ± 0.01.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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DDU417F8: Mechanotransducer currents in OHCs from Pls1 KO mice. (A, B) Saturating transducer currents recorded from a P5 het (A) and Pls1 KO (B) apical-coil OHC by applying a 50-Hz sinusoidal force stimuli to the hair bundles at the potential of −121 mV and +99 mV. The driver voltage (DV) signal of ±40 V to the fluid jet is shown above the traces (negative deflections of the DV are inhibitory). The arrows indicate the closure of the transducer channels, i.e. disappearance of the resting current, during inhibitory bundle displacements at −121 mV and +99 mV, respectively. Dashed lines indicate the holding current. (C) Peak-to-peak current–voltage curves were obtained from 7 het and 12 Pls1 KO OHCs (P5–P8) using 1.3 mm extracellular Ca2+. The fits through the data are according to Equation 1 (see Material and methods) with values: het k = 418 ± 33, Vr = 1.3 ± 0.3 mV, Vs = 38 ± 2 mV and γ = 0.42 ± 0.01; Pls1 KO k = 418 ± 40, Vr = 1.1 ± 0.4 mV, Vs = 40 ± 3 mV and γ = 0.41 ± 0.01.
Mentions: Besides its role in maintaining the morphology and structure of adult hair cell stereocilia, plastin 1 may be important for mechanoelectrical transduction. To test this, mechanoelectrical transducer (MET) currents were recorded from P5–P8 apical-coil OHCs by displacing their hair bundles in the excitatory and inhibitory direction using a piezo-driven fluid-jet (26,27). The apparent overall steady-state stiffness of the hair bundle measured in het OHCs (6.3 ± 0.6 mN/m, n = 16) was similar to that of Pls1 KO cells (8.3 ± 1.0 mN/m, n = 11) and comparable with that measured from wild-type mouse OHCs in organotypic cultures (28). Upon moving the bundles towards the taller stereocilia (i.e. in the excitatory direction) and at negative membrane potentials, a large inward MET current could be elicited in OHCs from both het and Pls1 KO mice (Fig. 8A and B). The maximum MET current was found to be similar between het (−937 ± 46 pA at −81 mV, n = 7) and KO cells (−843 ± 34 pA at −81 mV, n = 12). Any resting current flowing through open MET channels in the absence of mechanical stimulation was reduced when bundles were moved towards the shorter stereocilia (i.e. in the inhibitory direction) in all het and Pls1 KO OHCs (Fig. 8A and B, arrows). Because the MET current reverses near 0 mV, it became outward when excitatory bundle stimulation was applied during voltage steps positive to its reversal potential (Fig. 8A–C). At positive potentials, the larger resting transducer current (e.g. at +99 mV in Fig. 8A and B: arrows) is due to an increased open probability of the transducer channel resulting from a reduced driving force for Ca2+ influx (29,30). The above-mentioned results indicate that the biophysical properties of the transducer channel, including the presence of a resting current, are not affected by the absence of plastin 1.Figure 8.

Bottom Line: Several actin-associated proteins are essential for stereocilia formation and maintenance, and their absence leads to deafness.Auditory hair cells developed normally in Pls1 KO, but in young adult animals, the stereocilia of inner hair cells were reduced in width and length.These results show that in contrast to other actin-bundling proteins such as espin, harmonin or Eps8, plastin 1 is dispensable for the initial formation of stereocilia.

View Article: PubMed Central - PubMed

Affiliation: Centre for Auditory Research, UCL Ear Institute, University College London, London, UK.

Show MeSH
Related in: MedlinePlus