Developmental Changes in Two Voltage-Dependent Sodium Currents in Utricular Hair Cells

2007 ◽  
Vol 97 (2) ◽  
pp. 1684-1704 ◽  
Author(s):  
Julian R. A. Wooltorton ◽  
Sophie Gaboyard ◽  
Karen M. Hurley ◽  
Steven D. Price ◽  
Jasmine L. Garcia ◽  
...  
Keyword(s):  
Hair Cells ◽  
Sodium Current ◽  
Na Channel ◽  
Type I ◽  
Voltage Range ◽  
Negative Voltage ◽  
Vestibular Hair Cells ◽  
Voltage Dependent ◽  
Channel Expression ◽  
I Cells

Two kinds of sodium current ( INa) have been separately reported in hair cells of the immature rodent utricle, a vestibular organ. We show that rat utricular hair cells express one or the other current depending on age (between postnatal days 0 and 22, P0—P22), hair cell type (I, II, or immature), and epithelial zone (striola vs. extrastriola). The properties of these two currents, or a mix, can account for descriptions of INa in hair cells from other reports. The patterns of Na channel expression during development suggest a role in establishing the distinct synapses of vestibular hair cells of different type and epithelial zone. All type I hair cells expressed INa,1, a TTX-insensitive current with a very negative voltage range of inactivation (midpoint: −94 mV). INa,2 was TTX sensitive and had less negative voltage ranges of activation and inactivation (inactivation midpoint: −72 mV). INa,1 dominated in the striola at all ages, but current density fell by two-thirds after the first postnatal week. INa,2 was expressed by 60% of hair cells in the extrastriola in the first week, then disappeared. In the third week, all type I cells and about half of type II cells had INa,1; the remaining cells lacked sodium current. INa,1 is probably carried by NaV1.5 subunits based on biophysical and pharmacological properties, mRNA expression, and immunoreactivity. NaV1.5 was also localized to calyx endings on type I hair cells. Several TTX-sensitive subunits are candidates for INa,2.

Evidence for an Na+-K+-Cl−cotransporter in mammalian type I vestibular hair cells

1997 ◽  
Vol 273 (6) ◽  
pp. C1972-C1980 ◽  
Author(s):  
K. J. Rennie ◽  
J. F. Ashmore ◽  
M. J. Correia
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Cell Swelling ◽  
Type I ◽  
Vestibular Hair Cells ◽  
Type I Cells ◽  
High K ◽  
I Cells ◽  
Shape Changes ◽  
External K

In amniotes, there are two types of hair cells, designated I and II, that differ in their morphology, innervation pattern, and ionic membrane properties. Type I cells are unique among hair cells in that their basolateral surfaces are almost completely enclosed by an afferent calyceal nerve terminal. Recently, several lines of evidence have ascribed a motile function to type I hair cells. To investigate this, elevated external K+, which had been used previously to induce hair cell shortening, was used to induce shape changes in dissociated mammalian type I vestibular hair cells. Morphologically identified type I cells shortened and widened when the external K+ concentration was raised isotonically from 2 to 125 mM. The shortening did not require external Ca2+ but was abolished when external Cl− was replaced with gluconate or sulfate and when external Na+ was replaced with N-methyl-d-glucamine. Bumetanide (10–100 μM), a specific blocker of the Na+-K+-Cl− cotransporter, significantly reduced K+-induced shortening. Hyposmotic solution resulted in type I cell shape changes similar to those seen with high K+, i.e., shortening and widening. Type I cells became more spherical in hyposmotic solution, presumably as a result of a volume increase due to water influx. In hypertonic solution, cells became narrower and increased in length. These results suggest that shape changes in type I hair cells induced by high K+ are due, at least in part, to ion and solute entry via an Na+-K+-Cl− cotransporter, which results in cell swelling. A scheme is proposed whereby the type I hair cell depolarizes and K+ leaves the cell via voltage-dependent K+channels and accumulates in the synaptic space between the type I hair cell and calyx. Excess K+ could then be removed from the intercellular space by uptake via the cotransporter.

A delayed rectifier conductance in type I hair cells of the mouse utricle

1996 ◽  
Vol 76 (2) ◽  
pp. 995-1004 ◽  
Author(s):  
A. Rusch ◽  
R. A. Eatock
Keyword(s):  
Hair Cells ◽  
Time Course ◽  
Dissociation Constants ◽  
Resting Potential ◽  
Delayed Rectifier ◽  
Type I ◽  
Type Ii ◽  
Voltage Range ◽  
Average Maximum

1. Membrane currents of hair cells in acutely excised or cultured mouse utricles were recorded with the whole cell voltage-clamp method at temperatures between 23 and 36 degrees C. 2. Type I and II hair cells both had delayed rectifier conductances that activated positive to -55 mV. 3. Type I, but not type II, hair cells had an additional delayed rectifier conductance (gK,L) with an activation range that was unusually negative and variable. At 23-25 degrees C, V(1/2) values ranged from -88 to -62 mV in 57 cells. 4. gK,L was very large. At 23-25 degrees C, the average maximum chord conductance was 75 +/- 65 nS (mean +/- SD, n = 57; measured at -54 mV), or approximately 21 nS/pF of cell capacitance. 5. gK,L was highly selective for K+ over Na+ (permeability ratio PNa+/PK+:0.006), but unlike other delayed rectifiers, gK,L was significantly permeable to Cs+ (PCs+/PK+:0.31). gK,L was independent of extracellular Ca2+. 6. At -64 mV, Ba2+ and 4-aminopyridine blocked gK,L with apparent dissociation constants of 2.0 mM and 43 microM, respectively. Extracellular Cs+ (5 mM) blocked gK,L by 50% at -124 mV. Apamin (100 nM) and dendrotoxin (10 nM) has no effect. 7. The kinetic data of gK,L are consistent with a sequential gating model with at least two closed states and one open state. The slow activation kinetics (principal time constants at 23-25 degrees C:600-200 ms) had a thermal Q10 of 2.1. Inactivation (Q10:2.7) was partial at all temperatures. Deactivation followed a double-exponential time course and had a Q10 of 2.0. 8. At 23-25 degrees C, gK,L was appreciably activated at the mean resting potential of type I hair cells (-77 +/- 3.1 mV, n = 62), so that input conductances were often more than an order of magnitude larger than those of type II cells. If these conditions hold in vivo, type I cells would produce unusually small receptor potentials. Warming the cells to 36 degrees C produced parallel shifts in gK,L's activation range (0.8 +/- 0.3 mV/degrees C, n = 8), and in the resting potential (0.6 +/- 0.3 mV/degrees C, n = 4). Thus the high input conductances were not an artifact of unphysiological temperatures but remained high near body temperature. It remains possible that in vivo gK,L's activation range is less negative and input conductances are lower; the large variance in the voltage range of activation suggests that it may be subject to modulation.

Ionic Currents and Electromotility in Inner Ear Hair Cells From Humans

1998 ◽  
Vol 79 (4) ◽  
pp. 2235-2239 ◽  
Author(s):  
John S. Oghalai ◽  
Jeffrey R. Holt ◽  
Takashi Nakagawa ◽  
Thomas M. Jung ◽  
Newton J. Coker ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Ionic Currents ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Sensory Receptor ◽  
Surgical Removal ◽  
Type I ◽  
Vestibular Hair Cells ◽  
Sensory Receptor Cells

Oghalai, John S., Jeffrey R. Holt, Takashi Nakagawa, Thomas M. Jung, Newton J. Coker, Herman A. Jenkins, Ruth Anne Eatock, and William E. Brownell. Ionic currents and electromotility in inner ear hair cells from humans. J. Neurophysiol. 79: 2235–2239, 1998. The upright posture and rich vocalizations of primates place demands on their senses of balance and hearing that differ from those of other animals. There is a wealth of behavioral, psychophysical, and CNS measures characterizing these senses in primates, but no prior recordings from their inner ear sensory receptor cells. We harvested human hair cells from patients undergoing surgical removal of life-threatening brain stem tumors and measured their ionic currents and electromotile responses. The hair cells were either isolated or left in situ in their sensory epithelium and investigated using the tight-seal, whole cell technique. We recorded from both type I and type II vestibular hair cells under voltage clamp and found four voltage-dependent currents, each of which has been reported in hair cells of other animals. Cochlear outer hair cells demonstrated electromotility in response to voltage steps like that seen in rodent animal models. Our results reveal many qualitative similarities to hair cells obtained from other animals and justify continued investigations to explore quantitative differences that may be associated with normal or pathological human sensation.

Molecular characterization of an inward rectifier channel (IKir) found in avian vestibular hair cells: cloning and expression of pKir2.1

2004 ◽  
Vol 19 (2) ◽  
pp. 155-169 ◽  
Author(s):  
Manning J. Correia ◽  
Thomas G. Wood ◽  
Deborah Prusak ◽  
Tianxiang Weng ◽  
Katherine J. Rennie ◽  
...  
Keyword(s):  
Hair Cells ◽  
Cho Cells ◽  
Dwell Time ◽  
Single Channel ◽  
Cloning And Expression ◽  
Single Type ◽  
Type I ◽  
Type Ii ◽  
Vestibular Hair Cells ◽  
Inwardly Rectifying

A fast inwardly rectifying current has been observed in some of the sensory cells (hair cells) of the inner ear of several species. While the current was presumed to be an IKir current, contradictory evidence existed as to whether the cloned channel actually belonged to the Kir2.0 subfamily of potassium inward rectifiers. In this paper, we report for the first time converging evidence from electrophysiological, biochemical, immunohistochemical, and genetic studies that show that the Kir2.1 channel carries the fast inwardly rectifying currents found in pigeon vestibular hair cells. Following cytoplasm extraction from single type II and multiple pigeon vestibular hair cells, mRNA was reverse transcribed, amplified, and sequenced. The open reading frame (ORF), consisting of a 1,284-bp nucleotide sequence, showed 94, 85, and 83% identity with Kir2.1 subunit sequences from chick lens, Kir2 sequences from human heart, and a mouse macrophage cell line, respectively. Phylogenetic analyses revealed that pKir2.1 formed an immediate node with hKir2.1 but not with hKir2.2–2.4. Hair cells (type I and type II) and supporting cells in the sensory epithelium reacted positively with a Kir2.1 antibody. The whole cell current recorded in oocytes and CHO cells, transfected with pigeon hair cell Kir2.1 (pKir2.1), demonstrated blockage by Ba2+ and sensitivity to changing K+ concentration. The mean single-channel linear slope conductance in transfected CHO cells was 29 pS. The open dwell time was long (∼300 ms at −100 mV), and the closed dwell time was short (∼34 ms at −100 mV). Multistates ranging from 3–6 were noted in some single-channel responses. All of the above features have been described for other Kir2.1 channels. Current clamp studies of native pigeon vestibular hair cells illustrated possible physiological roles of the channel and showed that blockage of the channel by Ba2+ depolarized the resting membrane potential by ∼30 mV. Negative currents hyperpolarized the membrane ∼20 mV before block but ∼60 mV following block. RT-PCR studies revealed that the pKir2.1 channels found in pigeon vestibular hair cells were also present in pigeon vestibular nerve, vestibular ganglion, lens, neck muscle, brain (brain stem, cerebellum and optic tectum), liver, and heart.

scholarly journals Zfhx3 Transcription Factor Represses the Expression of SCN5A Gene and Decreases Sodium Current Density (INa)

2021 ◽  
Vol 22 (23) ◽  
pp. 13031
Author(s):  
Marcos Rubio-Alarcón ◽  
Anabel Cámara-Checa ◽  
María Dago ◽  
Teresa Crespo-García ◽  
Paloma Nieto-Marín ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cardiac Tissue ◽  
Sodium Current ◽  
Na Channel ◽  
Ubiquitin Protein Ligase ◽  
Endogenous Expression ◽  
Voltage Dependent ◽  
Familial Atrial Fibrillation ◽  
Cardiac Excitability ◽  
Scn5a Gene

The ZFHX3 and SCN5A genes encode the zinc finger homeobox 3 (Zfhx3) transcription factor (TF) and the human cardiac Na+ channel (Nav1.5), respectively. The effects of Zfhx3 on the expression of the Nav1.5 channel, and in cardiac excitability, are currently unknown. Additionally, we identified three Zfhx3 variants in probands diagnosed with familial atrial fibrillation (p.M1260T) and Brugada Syndrome (p.V949I and p.Q2564R). Here, we analyzed the effects of native (WT) and mutated Zfhx3 on Na+ current (INa) recorded in HL-1 cardiomyocytes. ZFHX3 mRNA can be detected in human atrial and ventricular samples. In HL-1 cardiomyocytes, transfection of Zfhx3 strongly reduced peak INa density, while the silencing of endogenous expression augmented it (from −65.9 ± 8.9 to −104.6 ± 10.8 pA/pF; n ≥ 8, p < 0.05). Zfhx3 significantly reduced the transcriptional activity of human SCN5A, PITX2, TBX5, and NKX25 minimal promoters. Consequently, the mRNA and/or protein expression levels of Nav1.5 and Tbx5 were diminished (n ≥ 6, p < 0.05). Zfhx3 also increased the expression of Nedd4-2 ubiquitin-protein ligase, enhancing Nav1.5 proteasomal degradation. p.V949I, p.M1260T, and p.Q2564R Zfhx3 produced similar effects on INa density and time- and voltage-dependent properties in WT. WT Zfhx3 inhibits INa as a result of a direct repressor effect on the SCN5A promoter, the modulation of Tbx5 increasing on the INa, and the increased expression of Nedd4-2. We propose that this TF participates in the control of cardiac excitability in human adult cardiac tissue.

Electrically Evoked Motile Responses of Mammalian Type I Vestibular Hair Cells

1992 ◽  
Vol 2 (3) ◽  
pp. 181-191
Author(s):  
Hans Peter Zenner ◽  
Günter Reuter ◽  
Shi Hong ◽  
Ulrike Zimmermann ◽  
Alfred H. Gitter
Keyword(s):  
Hair Cells ◽  
Sensory Modality ◽  
Outer Hair Cells ◽  
Type I ◽  
Image Subtraction ◽  
Low Frequencies ◽  
Vestibular Hair Cells ◽  
Mechanical Responses ◽  
Contrast Enhanced ◽  
Length Changes

Vestibular hair cells, type I and II, with membrane potentials around -64 mV were prepared from guinea pig ampullar cristae and maculae. In type I cells, current injection, application of voltage steps during membrane patch-clamping, or extracellular alternating current (ac) fields evoked fast length changes of 50 nm to 500 nm of the cell “neck”. Mechanical responses were determined by computerized video techniques with contrast-enhanced digital image subtraction (DIS) and interpeak pixel counts (IPPC) or by double photodiode measurements. These techniques allowed spatial resolutions of 300 nm, 120 nm, and 50 nm, respectively. In contrast to measurements of high-frequency movements of auditory outer hair cells (OHCs), the mechanical responses of type I VHCs were restricted to low frequencies below 85 Hz. In addition to recently reported slow motility of VHCs, the present results suggest that fast mechanical VHC responses could significantly influence macular and cupular mechanics. Isometric and isotonic variants are discussed. The observed frequency maxima gap between VHCs and OHCs is suggested to contribute to a clear separation of the auditory and the vestibular sensory modality.

Temporal Bone Studies of the Human Peripheral Vestibular System

2000 ◽  
Vol 109 (5_suppl) ◽  
pp. 20-25 ◽  
Author(s):  
Kojiro Tsuji ◽  
Steven D. Rauch ◽  
Conrad Wall ◽  
Luis Velázquez-Villaseñor ◽  
Robert J. Glynn ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Ganglion Cells ◽  
Significant Loss ◽  
Small Sample ◽  
Type I ◽  
Type Ii ◽  
Vestibular Hair Cells ◽  
Scarpa's Ganglion ◽  
Temporal Bones

Quantitative assessments of vestibular hair cells and Scarpa's ganglion cells were performed on 17 temporal bones from 10 individuals who had well-documented clinical evidence of aminoglycoside ototoxicity (streptomycin, kanamycin, and neomycin). Assessment of vestibular hair cells was performed by Nomarski (differential interference contrast) microscopy. Hair cell counts were expressed as densities (number of cells per 0.01 mm2 surface area of the sensory epithelium). The results were compared with age-matched normal data. Streptomycin caused a significant loss of both type I and type II hair cells in all 5 vestibular sense organs. In comparing the ototoxic effect on type I versus type II hair cells, there was greater type I hair cell loss for all 3 cristae, but not for the maculae. The vestibular ototoxic effects of kanamycin appeared to be similar to those of streptomycin, but the small sample size precluded definitive conclusions from being made. Neomycin did not cause loss of vestibular hair cells. Within the limits of this study (maximum postototoxicity survival time of 12 months), there was no significant loss of Scarpa's ganglion cells for any of the 3 drugs. The findings have implications in several clinical areas, including the correlation of vestibular test results to pathological findings, the rehabilitation of patients with vestibular ototoxicity, the use of aminoglycosides to treat Meniere's disease, and the development of a vestibular prosthesis.

Inward potassium rectifier current in type I vestibular hair cells isolated from guinea pig

1993 ◽  
Vol 149 (1) ◽  
pp. 51-55 ◽  
Author(s):  
Corinne Griguer ◽  
Alain Sans ◽  
Jean Valmier ◽  
Jacques Lehouelleur
Keyword(s):  
Guinea Pig ◽  
Hair Cells ◽  
Type I ◽  
Vestibular Hair Cells
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