Linking LIMK1 deficiency to hyperacusis and progressive hearing loss in individuals with Williams syndrome

Matsumoto, Nozomu; Kitani, Rei; Kalinec, Federico

doi:10.4161/cib.4.2.14491

Cited by 23 publications

(17 citation statements)

References 27 publications

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“…It encodes a serine/threonine kinase, which regulates outer hair cell motility by its effect on actin (Stanyon & Bernard, 1999). Matsumoto, Kitani, and Kalinec (2011) proposed that a deficiency of LIMK 1 might cause an increase in outer hair cell motility, leading to increased amplification of sound and thus to hyperacusis (Matsumoto, Kitani, & Kalinec, 2011). The interpretation of the startle reflex in hyperacusis is not clear.…”

Section: Williams Syndrome and A Possible Genetic Linkmentioning

confidence: 99%

“…In addition to auditory anomalies such as hyperacusis (Attias, Raveh, Ben-Naftali, Zarchi, & Gothelf, 2008;Elsabbagh, Cohen, Cohen, Rosen, & Karmiloff-Smith, 2011;Levitin, Cole, Lincoln, & Bellugi, 2005;Matsumoto et al, 2011), other reported phenomena in Williams syndrome include auditory allodynia (Levitan & Bellugi, 1998;Levitan et al, 2005Levitan et al, , 2003Miani, Passon, Bracale, Barotti, & Panzolli, 2001). Cortical anatomical abnormalities have in part been attributed to reduced volume and altered sulcal morphology of the Sylvian fissure, atypical primary auditory cortex cytoarchitecture, and increased volume of the superior temporal gyrus.…”

Section: Dtimentioning

confidence: 99%

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A Review of Hyperacusis and Future Directions: Part I. Definitions and Manifestations

et al. 2014

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Section: Williams Syndrome and A Possible Genetic Linkmentioning

confidence: 99%

Section: Dtimentioning

confidence: 99%

A Review of Hyperacusis and Future Directions: Part I. Definitions and Manifestations

et al. 2014

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“…In addition, they are able to elongate and shorten at frequencies of up to 100 kHz-and presumably beyond that-after electrical stimulation (4,5). This motile response, usually referred to as OHC electromotility, is a crucial component of the cochlear amplifier, the active process that enhances sensitivity and frequency discrimination in the mammalian inner ear (6)(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Microdomains Shift and Rotate in the Lateral Wall of Cochlear Outer Hair Cells

Kitani

Park

Kalinec

2013

Biophysical Journal

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Outer hair cell (OHC) electromotility, a response consisting of reversible changes in cell length and diameter induced by electrical stimulation, confers remarkable sensitivity and frequency resolution to the mammalian inner ear. Looking for a better understanding of this mechanism, we labeled isolated guinea pig OHCs with microspheres and, using high-speed video recording, investigated their movements at the apical, mid, and basal regions of osmotically and electrically stimulated cells. After hypoosmotic challenge, OHCs shortened and their diameter increased, with microspheres moving always toward the central plane; iso-osmolarity returned OHCs to their original shape and microspheres to their original positions. Under electrical stimulation, microspheres exhibited robust movements, with their displacement vectors changing in direction from random to parallel to the longitudinal axis of the cells with peak reorientation speeds of up to 6 rad/s and returning to random after 5 min without stimulation. Alterations in plasma-membrane cholesterol levels as well as cytoskeleton integrity affected microsphere responses. We concluded that microspheres attach to different molecular microdomains, and these microdomains are able to shift and rotate in the plane of the OHC lateral wall with a dynamics tightly regulated by membrane lipid composition and the cortical cytoskeleton.

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“…OHCs were whole-cell voltage clamped with an Axon 200B amplifier using patch pipettes having initial resistances of 3-5 MΩ. Series resistances ranged from 5 to 20 MΩ [26,27]. All data acquisition and analysis were performed with a Windows-based patch clamp program, jClamp.…”

Section: Whole-cell Patch Clampmentioning

confidence: 99%

Effects of cholesterol alterations are mediated via G-protein-related pathways in outer hair cells

Nagaki

Kakehata

Kitani

et al. 2013

Pflugers Arch - Eur J Physiol

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Cholesterol is an essential component of cell membranes, and determines their rigidity and fluidity. Alterations in membrane cholesterol by MβCD or water-soluble cholesterol affect the stiffness, capacitance, motility, and cell length of outer hair cells (OHCs). This suggests that reconstruction of the cytoskeleton may be induced by cholesterol alterations. In this study, we investigated intracellular signaling pathways involving G proteins to determine whether they modulate the changes in voltage-dependent capacitance caused by cholesterol alterations. Membrane capacitance of isolated guinea pig OHCs were assessed using a two-sine voltage stimulus protocol superimposed onto a voltage ramp (200 ms duration) from −150 to +140 mV. One group of OHCs was treated with 100 μM guanosine 5′-O-(3-thiotriphosphate) tetralithium salt (GTPγS), the GTP analog, administrated into individual cells via patch pipettes. Another group of OHCs was internally perfused with 600 μM guanosine 5′-(β-thio) diphosphate trilithium salt (GDPβS), the GDP analog. A third group was perfused with internal solution only as a control. Application of 1 mM MβCD shifted non-linear capacitance curves to the depolarized direction of the control group with reduction of the peak capacitance (C mpeak ). After the 10-min application of MβCD, shifts of voltage at C mpeak (V cmpeak ) and reduction of C mpeak were 73.32±11.09 mV and 9.09±2.10 pF, respectively (n=4). On the other hand, in the GTPγS-treated group, the shift of V cmpeak and reduction of C mpeak were attenuated remarkably. The shift of V cmpeak and reduction of C mpeak in the 10-min application of MβCD were 9.73± 10.92 mV and 3.08±1.91 pF, respectively (n=7). MβCD decreased the cell length by 16.53±4.27 % in the control group and by 6.45±6.22 % in the GTPγS group. In addition, we investigated the effects of GDPβS on cholesteroltreated OHCs. One millimolar cholesterol was externally applied after the 4-min application of 1 mM MβCD because the shift of V-C m function caused by cholesterol alone was small. Application of cholesterol shifted V-C m curves of the control group to the hyperpolarized direction with increase of the C mpeak . After the 10-min application of cholesterol, changes of V cmpeak and C mpeak were −9.19±6.68 mV and 2.14±0.44 pF, respectively (n=4). On the other hand, in the GDPβS-treated OHCs, the shift of V cmpeak and increase of C mpeak were attenuated markedly. The shift of V cmpeak and increase of C mpeak after 10 min were 5.13±10.46 mV and −0.55±1.39 pF, respectively (n=6). This study demonstrated that internally perfused GTPγS inhibited the MβCD effects and GDPβS inhibited the cholesterol effects, raising the possibility that G proteins may be involved in outer hair cell homeostasis as well as the possibility that cholesterol response may be G protein mediated. More study is required to clarify the detailed role of G proteins in the relation between cholesterol and the OHC cytoskeleton.

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Linking LIMK1 deficiency to hyperacusis and progressive hearing loss in individuals with Williams syndrome

Cited by 23 publications

References 27 publications

A Review of Hyperacusis and Future Directions: Part I. Definitions and Manifestations

A Review of Hyperacusis and Future Directions: Part I. Definitions and Manifestations

Microdomains Shift and Rotate in the Lateral Wall of Cochlear Outer Hair Cells

Effects of cholesterol alterations are mediated via G-protein-related pathways in outer hair cells

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