Computational model of vectorial potassium transport by cochlear marginal cells and vestibular dark cells

2007 ◽  
Vol 292 (1) ◽  
pp. C591-C602 ◽  
Author(s):  
Imran H. Quraishi ◽  
Robert M. Raphael
Keyword(s):  
Ion Transport ◽  
Inner Ear ◽  
Short Circuit ◽  
Ion Homeostasis ◽  
Bartter Syndrome ◽  
Dark Cell ◽  
Dark Cells ◽  
Type Iv ◽  
Marginal Cells ◽  
Vestibular Dark Cells

Cochlear marginal cells and vestibular dark cells transport potassium into the inner ear endolymph, a potassium-rich fluid, the homeostasis of which is essential for hearing and balance. We have formulated an integrated mathematical model of ion transport across these epithelia that incorporates the biophysical properties of the major ion transporters and channels located in the apical and basolateral membranes of the constituent cells. The model is constructed for both open- and short-circuit situations to test the extremes of functional capacity of the epithelium and predicts the steady-state voltages, ion concentrations, and transepithelial currents as a function of various transporter and channel densities. We validate the model by establishing that the cells are capable of vectorial ion transport consistent with several experimental measurements. The model indicates that cochlear marginal cells do not make a significant direct contribution to the endocochlear potential and illustrates how changes to the activity of specific transport proteins lead to reduced K+ flux across the marginal and dark cell layers. In particular, we investigate the mechanisms of loop diuretic ototoxicity and diseases with hearing loss in which K+ and Cl− transport are compromised, such as Jervell and Lange-Nielsen syndrome and Bartter syndrome, type IV, respectively. Such simulations demonstrate the utility of compartmental modeling in investigating the role of ion homeostasis in inner ear physiology and pathology.

Formation and Fate of the Otoconia

1973 ◽  
Vol 82 (1) ◽  
pp. 23-35 ◽  
Author(s):  
David J. Lim
Keyword(s):  
Calcium Carbonate ◽  
Organic Matrix ◽  
Laboratory Animals ◽  
Dark Cell ◽  
Gelatin Matrix ◽  
Dark Cells ◽  
The Matrix ◽  
Electron Microscopes ◽  
Vestibular Dark Cells ◽  
Clinical Conditions

Although mammalian otoconia are known to be composed of calcium carbonate in calcite form, their morphogenesis, maintenance, and fate are not well understood. More information on these problem areas would aid considerably in better understanding various clinical conditions, such as cupulolithiasis and otolith degeneration. This study was intended to clarify the fine morphology of the otolith in normal and adverse conditions in laboratory animals with the use of the scanning and transmission electron microscopes. It was confirmed by this study that the mammalian otoconium is composed of an organic matrix and minerals (calcium carbonate). When the minerals are removed by decalcification, or chelation, a well arranged organic matrix, and even a nucleus, can be found in the crystal. The matrix of the crystal is identical to the gelatin matrix of the otolithic membrane. This finding supports the possibility that a normal protein matrix is a prerequisite for normal otoconia formation, and that the exchange of calcium ions can occur without altering the crystal structure. The vestibular dark cells, which are thought to be endolymph-secreting cells, appear to be capable of removing calcium from the otoconia that are attached to the dark cell surfaces. Although this evidence is only circumstantial, its consistency is impressive. On the basis of the foregoing, it is tempting to speculate that the dark cells participate in the removal of the dislodged otoliths, but further study is required to ascertain this point.

scholarly journals Distribution of immunoreactive alpha- and beta-subunit isoforms of Na,K-ATPase in the gerbil inner ear.

1994 ◽  
Vol 42 (7) ◽  
pp. 843-853 ◽  
Author(s):  
J P McGuirt ◽  
B A Schulte
Keyword(s):  
Inner Ear ◽  
Cell Types ◽  
Beta Subunit ◽  
Atpase Subunit ◽  
New Information ◽  
Positive Immunostaining ◽  
Subunit Isoforms ◽  
Marginal Cells ◽  
Ganglion Neurons ◽  
Vestibular Dark Cells

Biochemical and histochemical studies have demonstrated abundant Na,K-ATPase in the inner ear and provided new information concerning the ion transport capacities of specialized cell types. To extend these earlier observations, we immunostained inner ears from adult gerbils with antibodies specific for the three known alpha- and the two known beta-isoforms of Na,K-ATPase. Different inner ear cell types contained specific and distinct combinations of alpha- and beta-subunit isoforms. Strial marginal cells and vestibular dark cells expressed the alpha 1- and beta 2-isoforms, whereas other positive epithelial cells expressed alpha 1 in combination with beta 1. Ganglion neurons and their peripheral processes showed positive immunostaining for the alpha 3- and beta 1-subunit isoforms. Subpopulations of fibrocytes in the spiral prominence, suprastrial and supralimbal regions, and vestibular system expressed either the alpha 1- or alpha 2-isoform, or both. The differential expression of Na,K-ATPase subunit isoforms presumably reflects different K+ and Na+ transport capacities among inner ear cell types which, working in concert, serve to generate and maintain the unique ionic and electrical environment in the mammalian inner ear.

Inhibitory Effect of Erythromycin on Ion Transport by Stria Vascularis and Vestibular Dark Cells

1996 ◽  
Vol 116 (4) ◽  
pp. 572-575 ◽  
Author(s):  
Jianzhong Liu ◽  
Daniel C. Marcus ◽  
Toshimitsu Kobayashi
Keyword(s):  
Ion Transport ◽  
Stria Vascularis ◽  
Inhibitory Effect ◽  
Dark Cells ◽  
Vestibular Dark Cells

P2U purinergic receptor inhibits apical IsK/KvLQT1 channel via protein kinase C in vestibular dark cells

1997 ◽  
Vol 273 (6) ◽  
pp. C2022-C2029 ◽  
Author(s):  
Daniel C. Marcus ◽  
Hiroshi Sunose ◽  
Jianzhong Liu ◽  
Zhijun Shen ◽  
Margaret A. Scofield
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Purinergic Receptor ◽  
Short Circuit ◽  
Specific Response ◽  
Gene Transcript ◽  
Whole Cell ◽  
Dark Cells ◽  
Kinase C ◽  
Vestibular Dark Cells

Vestibular dark cells (VDC) are known to electrogenically secrete K+ via slowly activating K+(IsK) channels, consisting of IsK regulatory and KvLQT1 channel subunits, and the associated short-circuit current ( I sc) is inhibited by agonists of the apical P2U(P2Y2) receptor (J. Liu, K. Kozakura, and D. C. Marcus. Audit. Neurosci. 2: 331–340, 1995). Measurements of relative K+ flux ( J K) with a self-referencing K+-selective probe demonstrated a decrease in J K after apical perfusion of 100 μM ATP. On-cell macropatch recordings from gerbil VDC showed a decrease of the IsKchannel current ( I IsK) by 83 ± 7% during pipette perfusion of 10 μM ATP. The magnitude of the decrease of I scby ATP was diminished in the presence of inhibitors of phospholipase C (PLC) and protein kinase C (PKC), U-73122 and GF109203X. Activation of PKC by phorbol 12-myristate 13-acetate (PMA, 20 nM) decreased I IsK by 79 ± 3% in perforated-patch whole cell recordings, whereas the inactive analog, 4α-PMA, had no effect. In contrast, elevation of cytosolic Ca2+ concentration by A-23187 increased the whole cell I IsK . The expression of the isk gene transcript was confirmed, and the serine responsible for the species-specific response to PKC was found to be present in the gerbil IsKsequence. These data provide evidence consistent with a direct effect of the PKC branch of the PLC pathway on the IsK channel of VDC in response to activation of the apical P2Ureceptor and predict that the secretion of endolymph in the human vestibular system may be controlled by PKC in the same way as in our animal model.

scholarly journals Immunohistochemical Localization of the Na-K-Cl Co-transporter (NKCC1) in the Gerbil Inner Ear

1997 ◽  
Vol 45 (6) ◽  
pp. 773-778 ◽  
Author(s):  
James J. Crouch ◽  
Nobuki Sakaguchi ◽  
Christian Lytle ◽  
Bradley A. Schulte
Keyword(s):  
Inner Ear ◽  
Stria Vascularis ◽  
Ion Homeostasis ◽  
Human Colon ◽  
Pcr Primers ◽  
Immunohistochemical Localization ◽  
Physiological Data ◽  
Spiral Ligament ◽  
Dark Cells ◽  
Specific Pcr

We mapped the cellular and subcellular distribution of the Na-K-Cl co-transporter (NKCC) in the adult gerbil inner ear by immunostaining with a monoclonal antibody (MAb T4) generated against human colon NKCC. Heavy immunolabeling was seen in the basolateral plasma membrane of marginal cells in the stria vascularis and dark cells in the vestibular system. Subpopulations of fibrocytes in the cochlear spiral ligament and limbus and underlying the vestibular neurosensory epithelium also stained with moderate to strong intensity, apparently along their entire plasmalemma. Because MAb T4 recognizes both the basolateral secretory (NKCC1) and the apical absorptive (NKCC2) isoforms of the co-transporter, we employed reverse transcription and the polymerase chain reaction (RT-PCR) to explore isoform diversity in inner ear tissues. Using NKCC1 and NKCC2 isoform-specific PCR primers based on mouse and human sequences, only transcripts for NKCC1 were detected in the gerbil inner ear. The presence of abundant NKCC1 in the basolateral plasmalemma of strial marginal and vestibular dark cells confirms conclusions drawn from pharmacological and physiological data. The co-expression of NKCC1 and Na,K-ATPase in highly specialized subpopulations of cochlear and vestibular fibrocytes provides further evidence for their role in recycling K+ leaked or effluxed through hair cells into perilymph back to endolymph, as postulated in current models of inner ear ion homeostasis.

scholarly journals Creatine kinase in epithelium of the inner ear.

1992 ◽  
Vol 40 (2) ◽  
pp. 185-192 ◽  
Author(s):  
S S Spicer ◽  
B A Schulte
Keyword(s):  
Creatine Kinase ◽  
Inner Ear ◽  
Vestibular System ◽  
Hair Cells ◽  
Stria Vascularis ◽  
Photoreceptor Cells ◽  
Cell Types ◽  
Dark Cells ◽  
Transitional Cells ◽  
Marginal Cells

Epithelium of the inner ear in the gerbil and mouse was examined immunocytochemically for presence of creatine kinase (CK). Marginal cells of the cochlear stria vascularis and dark cells and transitional cells of the vestibular system were found to contain an abundance of the MM isozyme (MM-CK). CK in these cells concurs with that which is coupled to Na,K-ATPase in other cells and is considered to supply ATP for the Na,K-ATPase that mediates the high KCl of endolymph. Inner hair cells revealed content of the BB isozyme and in this respect resembled the energy-transducing photoreceptor cells in retina. In addition, outer phalangeal (Deiters') cells stained for both MM- and BB-CK whereas inner phalangeal cells evidenced content of only the BB isozyme. Immunolocalization of CK appeared similar in mouse and gerbil inner ear. Specificity of the staining was affirmed by observations in agreement with those reported for CK in various cell types and by staining with antisera from more than one source.

Stria vascularis and vestibular dark cells: characterisation of main structures responsible for inner-ear homeostasis, and their pathophysiological relations

2008 ◽  
Vol 123 (2) ◽  
pp. 151-162 ◽  
Author(s):  
R R Ciuman
Keyword(s):  
Inner Ear ◽  
Volume Concentration ◽  
Current Knowledge ◽  
Stria Vascularis ◽  
Dark Cells ◽  
Adequate Response ◽  
Complex Process ◽  
And Function ◽  
Vestibular Dark Cells ◽  
Distinct Morphology

AbstractThe regulation of inner-ear fluid homeostasis, with its parameters volume, concentration, osmolarity and pressure, is the basis for adequate response to stimulation. Many structures are involved in the complex process of inner-ear homeostasis. The stria vascularis and vestibular dark cells are the two main structures responsible for endolymph secretion, and possess many similarities. The characteristics of these structures are the basis for regulation of inner-ear homeostasis, while impaired function is related to various diseases. Their distinct morphology and function are described, and related to current knowledge of associated inner-ear diseases. Further research on the distinct function and regulation of these structures is necessary in order to develop future clinical interventions.

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