A5083691330- Hearing, Cochlea, Tinnitus, Genetics
- Ion Channels and Receptors
- Hearing Loss and Rehabilitation
- Ion channel regulation and function
- Vestibular and auditory disorders
- Biochemical Analysis and Sensing Techniques
- Connexins and lens biology
- Marine animal studies overview
- Acoustic Wave Phenomena Research
- Antimicrobial Peptides and Activities
- Erythrocyte Function and Pathophysiology
- Speech and Audio Processing
- Music and Audio Processing
- Ear Surgery and Otitis Media
- Photoreceptor and optogenetics research
- Cancer-related molecular mechanisms research
- Lipid Membrane Structure and Behavior
- Neurobiology and Insect Physiology Research
- Advanced Sensor and Energy Harvesting Materials
- Calcium signaling and nucleotide metabolism
- Olfactory and Sensory Function Studies
- Electron Spin Resonance Studies
- Acoustic Wave Resonator Technologies
- Polydiacetylene-based materials and applications
- Bat Biology and Ecology Studies
University of Sussex
2015-2025
Sussex County Community College
2021
University Medical Center Groningen
2014-2016
University of Groningen
2003-2016
National Institutes of Health
2003
Hammersmith Hospital
2003
Imperial College London
2003
University of Washington
2003
Office of Naval Research
2003
National Institute on Deafness and Other Communication Disorders
2003
Hair cells in mouse cochlear cultures are selectively labeled by brief exposure to FM1-43, a styryl dye used study endocytosis and exocytosis. Real-time confocal microscopy indicates that entry is rapid via the apical surface. Cooling 4°C high extracellular calcium both reduce loading. Pretreatment with EGTA, condition breaks tip links prevents mechanotransducer channel gating, abolishes subsequent loading presence of calcium. Dye recovers after chelation time course similar described for...
Myosin-VIIA (MYO7A) is an unconventional myosin responsible for syndromic (Usher 1B) or nonsyndromic forms of deafness in humans when mutated. In the cochlea, MYO7A expressed hair cells, where it believed to act as motor protein tensioning mechanoelectrical transducer (MET) channels, thus setting their resting open probability ( P o ). However, direct evidence this unique role mature cells lacking. Here, we show that has a distinct being crucial structural integrity bundles. Postnatal...
The most serious side-effect of the widely used aminoglycoside antibiotics is irreversible intracellular damage to auditory and vestibular hair cells inner ear. mechanism entry into has not been unequivocally resolved. Here we report that extracellular dihydrostreptomycin only blocks mechano-electrical transducer channels mouse outer at negative membrane potentials, as previously shown, but also enters through these channels, which are located in cells' mechanosensory bundles....
The first step towards the generation of receptor potential in hair cells is gating transducer channels and subsequent flow current, induced by deflection stereocilia. We describe properties current outer neonatal mice. Less extensive observations on inner suggest that their currents have similar characteristics. bundles were stimulated force from a fluid jet. are largest found so far any cell, with chord conductance up to 9.2 nS at -84 mV. transfer function suggests channel has least two...
Developmental changes in electrophysiological membrane properties of mouse cochlear inner hair cells (IHCs) were studied from just after terminal differentiation up to functional maturity. As early as embryonic day 14.5 (E14.5) newly differentiated IHCs express a very small outward K+ current that is largely insensitive 4-aminopyridine (4-AP). One later the inward rectifier, IK1, first observed. These immature initially exhibit only slow graded voltage responses under clamp. From E17.5...
Graphical Abstract figure legend HCN channels play an evolutionarily conserved pacemaker role in renal pelvic smooth muscle (RPSM) of lower and higher order mammals. The function hyperpolarization-activated cation (HCN) pacemakers remains controversial. Renal trigger contractions that expel waste from the kidney, have been localized to these tissues. To date, however, mechanisms underlying RPSM activity remain elusive. was investigated both (top left) (bottom mammalian models, which exhibit...
Abstract The hair bundles of outer cells in the mature mouse cochlea possess three distinct cell‐surface specializations: tip links, horizontal top connectors, and tectorial membrane attachment crowns. Electron microscopy was used to study appearance maturation these link types examine additional structures transiently associated with developing bundle. At embryonic day 17.5 (E17.5), stereocilia are interconnected by fine lateral links have punctate elements distributed over their surface....
Vestibular hair cells (VHCs) and cochlear outer (OHCs) of neonatal mice were stimulated by a fluid jet directed at their stereociliary bundles. Relations between the force exerted jet, bundle displacement, resulting transducer current studied. The mean maximum conductance in VHCs (2.6 nS) was about half that OHCs (5.5 nS), with largest recorded values being 4.1 nS 9.2 nS, respectively. In some activity single, 112 pS channel observed, allowing an estimate number channels: up to 36 82 OHCs,...
1 The expression of K+ currents in mouse outer hair cells (OHCs) was investigated as a function developmental age between postnatal day (P) 0 and P26, using whole-cell patch clamp. 2 During the first week, slow outward current (IK,neo) expressed by all OHCs from apical coil cochlea. amplitude this increased greatly P0 P6. Then, at beginning second IK,neo decreased. At same time, P8 onwards, IK,n, characteristic mature OHCs, rapidly expressed. 3 IK,n coincided with onset electromotility cell...
1. Inner hair cells were mechanically isolated from the apical, low‐frequency region of guinea‐pig cochlea and maintained by superfusion with tissue‐culture medium. Membrane currents studied under voltage clamp, using whole‐cell recording mode patch‐clamp technique. 2. The mostly at 35‐38 degrees C to obtain realistic kinetics currents, relevant functioning these in vivo. 3. Isolated inner had resting potentials about ‐65 mV. Depolarizing steps a holding potential ‐80 mV resulted large time‐...
Developmental changes in the coupling between Ca2+ entry and exocytosis were studied mouse inner hair cells (IHCs) which, together with afferent endings, form primary synapse of mammalian auditory system. currents (ICa) membrane capacitance (DeltaCm) recorded using whole-cell voltage clamp from maintained at body temperature, physiological (1.3 mM) extracellular Ca2+. The magnitudes both ICa DeltaCm increased maturation embryonic stages until postnatal day 6 (P6). Subsequently, gradually...
Homozygote varitint-waddler (Va) mice, expressing a mutant isoform (A419P) of TRPML3 (mucolipin 3), are profoundly deaf and display vestibular pigmentation deficiencies, sterility, perinatal lethality. Here we show that the carrying an A419P mutation represents constitutively active cation channel can also be identified in native hair cells as distinct inwardly rectifying current. We hypothesize constitutive activation occurs result helix-breaking proline substitution transmembrane-spanning...
Summary Transient receptor potential (TRP) channels TRPC3 and TRPC6 are expressed in both sensory neurons cochlear hair cells. Deletion of or mice caused no behavioural phenotype, although loss a shift rapidly adapting (RA) mechanosensitive currents to intermediate-adapting dorsal root ganglion neurons. deficits light touch silenced half small-diameter expressing mechanically activated RA currents. Double TRPC3/TRPC6 knock-out also showed hearing impairment, vestibular defective auditory...
Significance In the inner ear, sensory receptor cells (hair cells) signal reception of sound. They do so by converting mechanical input, due to sound waves moving hair bundles on these cells, into electrical current through ion channels situated at tips bundles. To keep receptors operating their maximum sensitivity, declines rapidly, a process known as adaptation. nonmammalian vertebrates, Ca 2+ ions entering mechanosensitive drive adaptation, but it has been questioned whether this...
Immunocytochemical studies have shown that protocadherin-15 (PCDH15) and cadherin-23 (CDH23) are associated with tip links, structures thought to gate the mechanotransducer channels of hair cells in sensory epithelia inner ear. The present report describes functional structural analyses from Pcdh15av3J (av3J), Pcdh15av6J (av6J) Cdh23v2J (v2J) mice. av3J v2J mice carry point mutations predicted introduce premature stop codons transcripts for Pcdh15 Cdh23, respectively, av6J an in-frame...
Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both alpha1D (Cav1.3) Ca2+ Na+ currents that activate near resting potential, we examined whether these two conductances involved in shaping Both had extremely rapid activation kinetics, followed by fast complete voltage-dependent inactivation for...
Although the dynamics of cell membranes and associated structures is vital for function, little known due to lack suitable methods. We found, using scanning ion conductance microscopy, that microvilli, membrane projections supported by internal actin bundles, undergo a life cycle: fast height-dependent growth, relatively short steady state, slow height-independent retraction. The microvilli can aggregate into stable where state extended. suggest intrinsic combined with their ability make...
A screen for protein tyrosine phosphatases (PTPs) expressed in the chick inner ear yielded a high proportion of clones encoding an avian ortholog phosphatase receptor Q (Ptprq), receptor-like PTP. Ptprq was first identified as transcript upregulated rat kidney response to glomerular nephritis and has recently been shown be active against inositol phospholipids. An antibody intracellular domain Ptprq, anti-Ptprq, stains hair bundles mice chicks. In ear, distribution is almost identical that...
Myosin VIIA is expressed by sensory hair cells and has a primary structure predicting role in membrane trafficking turnover, processes that may underlie the susceptibility of to aminoglycoside antibiotics. [ 3 H]Gentamicin accumulation effects aminoglycosides were therefore examined cochlear cultures mice with different missense mutations myosin gene, Myo7a , see whether plays ototoxicity. Hair from homozygous mutant sh1 mice, mutation nonconserved region head, respond rapidly treatment...