Eye & orbit tumors anatomy, epidemiology, pathology by himani
Cochlear anatomy, function and pathology III
Transcript of Cochlear anatomy, function and pathology III
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Cochlear anatomy, function and pathology III
Professor Dave FurnessKeele University
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Aims and objectives of this lecture
• Focus (3) on the cochlear lateral wall and Reissner’s membrane:
– The spiral ligament
– The stria vascularis
– The endolymphatic potential and potassium recycling
– Reissner’s membrane
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Homeostatic mechanisms generate a battery called the endocochlear(endolymphatic) potential which drives the sensitive transduction process
80 mV
0 mV
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Fluid segregation
• The three chambers contain different fluids
• Endolymph, high in potassium, in scala media
• Perilymph, high in sodium, in scala vestibuliand scala tympani
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Transduction by inner hair cells• The driving voltage of endocochlear potential and cell
membrane potential rapidly depolarises the cell which produces neurotransmitter from the base
stimulus
response
+80 mV
-70 mV
0 mV
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Transduction to motion - the endocochlear potential powers the outer hair cell movement
stimulus
response
+80 mV
-70 mV
0 mV
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Vulnerability of BM tuning to furosemide which inhibits generation of the EP
From: Robles and Ruggero, Physiological Reviews 81, No. 3, 2001
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Structure of the lateral wall
Stria vascularis
Spiral ligament
Spiral prominence
Basilar crest
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The stria vascularis
• Consists of three layers of cells: basal, intermediate and marginal
• Contains numerous blood vessels and melanocytes in pigmented animals
• Expresses proteins involved in potassium recycling such as potassium channels and sodium/potassium ATPases
• Basal and intermediate cells are connected together by gap junctions, and basal cells to adjacent cells of the spiral ligament (fibrocytes) also by gap junctions
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Structure of the stria vascularis
Basal cell
Intermediate cells
Marginalcells
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Structure of the stria vascularis
Basal cell
Intermediate cells
Marginalcells
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The spiral ligament
• The ligament is a much neglected, yet important part of the cochlea
• It consists of extracellular matrix with several cell types in it and has a complex cytoarchitecture.
– The majority of cell types are called fibrocytes, of which there are five types
– There are also endothelial cells surrounding blood vessels/capillaries
– There are also root cells
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Fibrocyte types
Type I
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types
Type II
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Fibrocytes – five types
Type III
Type III
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Fibrocytes – five types
Type IV
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Fibrocytes – five types
Type V
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Sodium/potassium ATPase is localised to membrane processes
• Type II and type V cells possess many processes
• These strongly express the sodium/potassium ATPase and increase the surface area to increase the ability to exchange sodium and potassium
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Fibrocytes express a range of proteins -some associated with homeostasis
• Sodium/potassium ATPase
• Aquaporin
• Glutamate transporter
• Potassium channels
• Gap junctions
• Calcium binding proteins
• Connective tissue growth factors
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Fibrocyte protein expression is complex
• Each of these proteins has a different distribution
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Fibrocyte structural features
• Membranes of all types are thrown into folds, but especially type II and type V which also express the most sodium/potassium ATPase
• Type III fibrocytes have a honeycomb membrane surface and are the only types to express aquaporin
• However, they also possess thick actin cables and are considered ‘tension’ fibrocytes, maintaining BM tension
• Type IV fibrocytes are similar in appearance to type III but lack the ATPase, aquaporin and actin cables
• Type I fibrocytes have few membrane folds and possess some ATPase
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Fibrocyte membrane morphology is designed to increase surface area – type II
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Type III fibrocytes also have increased surface area and contain actin cables attaching to ecm
and the bony wall
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Root cells also contribute to homeostasis
• Root cells connect the outer sulcal cells to the ligament cells
• They possess potassium recycling proteins and are thought to assist in the recycling of potassium via the epithelial cell gap junction network
From: Jagger DJ et al. The Membrane Properties of Cochlear Root Cells are Consistent with Roles in Potassium Recirculation and Spatial Buffering. J Assoc Res Otolaryngol. 2010 Sep;11(3):435-48.
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The extracellular matrix of the ligament• Dominated by type II and type IX collagen but
also contains type IV and type V
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Ultrastructure of ligament ecm
Organised into thick and thin fibres and plaques of type II collagen connected by type IX collage fibrils
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Ligament and stria work together to generate EP and recycle potassium
• Potassium recycling is necessary for maintenance of:– The endocochlear potential
– Transduction by the hair cells
– Amplification by the OHCs
• Potassium ions follow at least two routes, both ending up passing through fibrocytes and then into the stria vascularis
• This is a highly energy-dependent, metabolic process
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Connexins
• Connexins play a vital role in the function of the lateral wall
• Connexin 26 and 30 are the dominant types and are localised to both stria vascularis and spiral ligament
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Distribution of connexins 26 and 31
From: Jagger and Forge, 2015, Cell and Tissue Research 360, 633-644
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Two potassium recycling routes
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Possible mechanism of potassium recycling and generation of the endocochlear potential
Hibino,and Kurachi. 2006. Molecular and Physiological Bases of the K+ Circulation in the Mammalian Inner Ear. Physiology Vol. 21 no. 5, 336-345
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Fibrocyte culture – one of the few cochlear cell types that can be grown long term in
vitro
• Fibrocytes are mesenchymal in origin
• This means they retain a capacity to divide, unlike hair cells and spiral ganglion neurones
• A bank of fibrocyte cultures has several uses:– Study the electrophysiology and their role in
generating the EP
– Develop stem cell/replacement cell therapy
– Investigate growth promoting factors to stimulate cell survival and proliferation in vivo
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Fibrocytes grown on well plates in 2D look very flat
They resemble fibroblasts
They do not have an endogenous fibrocytephenotype
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Fibrocyte cultures grown on hydrogels
Have a more fibrocytic appearance than when grown flat
Express characteristic proteins
Appear to form networks, perhaps with gap junctions between them
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Reissner’s membrane – the third border of the scala media
Left: Mahendrasingam et al., 2011, JARO; Right Hackney and Furness, Noise and its Pathophysiology (eds Luxon and Prasher, 2007, Wiley)
3 week old mouse8 week old guinea pig
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Reissner’s membrane
• Reissner’s membrane is required to separate endolymph from perilymph and so maintain the endocochlear potential
• Other functional roles are uncertain, but it appears to express epithelial sodium channels and chloride channels
• It is likely to be involved in homeostasis of sodium chloride between the scala media and the scala vestibuli/tympani
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Structure of Reissner’s membrane
Scala vestibuli surface, mesothelial
Scala media surface, endothelial
Tight junctions
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Summary
• The cochlear lateral wall plays a major role in cochlear function
• The cells present in the outer sulcus, spiral ligament and stria vascularis work together to recycle potassium and regenerate the endocochlear potential on a continuous basis
• The EP powers both transduction and amplification to maintain the sensitivity and frequency selectivity of the cochlea