A5019241764- Hearing, Cochlea, Tinnitus, Genetics
- Ion Channels and Receptors
- Hearing Loss and Rehabilitation
- Vestibular and auditory disorders
- Ion channel regulation and function
- Acoustic Wave Phenomena Research
- Biochemical Analysis and Sensing Techniques
- Connexins and lens biology
- Marine animal studies overview
- Cancer-related molecular mechanisms research
- Neuroscience of respiration and sleep
- Congenital heart defects research
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Erythrocyte Function and Pathophysiology
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Retinal Development and Disorders
- Ear Surgery and Otitis Media
- Neurobiology and Insect Physiology Research
- RNA Research and Splicing
- Underwater Vehicles and Communication Systems
- Photoreceptor and optogenetics research
- Bat Biology and Ecology Studies
- MicroRNA in disease regulation
University of Sheffield
2016-2025
Neuroscience Institute
2025
University of Sussex
2001-2016
University of Washington
2003
University of Groningen
2003
University of Pavia
1996-2001
University of Bristol
1999-2001
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...
Outer hair cells (OHCs) provide amplification in the mammalian cochlea using somatic force generation underpinned by voltage-dependent conformational changes of motor protein prestin. However, prestin must be gated membrane potential on a cycle-by-cycle basis and periodic component receptor may greatly attenuated low-pass filtering due to OHC time constant (τ(m)), questioning functional relevance this mechanism. Here, we measured τ(m) from OHCs with range characteristic frequencies (CF)...
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....
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...
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...
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....
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...
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...
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...
Hair cells of the mammalian cochlea are specialized for dynamic coding sound stimuli. The transduction waves into electrical signals depends upon mechanosensitive hair bundles that project from cell's apical surface. Each stereocilium within a bundle is composed uniformly polarized and tightly packed actin filaments. Several stereociliary proteins have been shown to be associated with development function known cause deafness in mice humans when mutated. growth stereociliar core dynamically...
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...
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...
From just after birth, mouse inner hair cells (IHCs) expressed a Ca(2+)-activated K(+) current that was reduced by intracellular BAPTA at concentrations >or= 1 mM. The block of this nifedipine suggests the direct involvement Ca(v)1.3 Ca(2+) channels in its activation. On basis high sensitivity to apamin (K(D) 360 pM) it identified as small-conductance (SK), probably SK2. A similar also found outer (OHCs) from beginning second postnatal week. In both cell types appearance SK coincided with...
The mammalian cochlea is specialized to recognize and process complex auditory signals with remarkable acuity temporal precision over a wide frequency range. quality of the information relayed afferent fibers mainly depends on transfer characteristics inner hair cell (IHC) ribbon synapses. To investigate biophysical properties synaptic machinery, we measured changes in membrane capacitance (Δ C m ) low-frequency (apical region, ∼300 Hz) high-frequency (basal, ∼30 kHz) gerbil IHCs maintained...
The deafness (dn) and Beethoven (Bth) mutant mice are models for profound congenital (DFNB7/B11) progressive hearing loss (DFNA36), respectively, caused by recessive dominant mutations of transmembrane cochlear-expressed gene 1 (TMC1), which encodes a protein unknown function. In the mouse cochlea Tmc1 is expressed in both outer (OHCs) inner (IHCs) hair cells from early stages development. Immature seem normal appearance biophysical properties. From around P8 OHCs P12 IHCs, mutants fail to...
Mammalian cochlear inner hair cells (IHCs) are specialized to process developmental signals during immature stages and sound stimuli in adult animals. These conveyed onto auditory afferent nerve fibres. Neurotransmitter release at IHC ribbon synapses is controlled by L-type Ca(V)1.3 Ca(2+) channels, the biophysics of which still unknown native mammalian cells. We have investigated localization elementary properties channels mouse IHCs under near-physiological recording conditions. cell...