Acute blockade of inner ear marginal and dark cell K+ secretion: Effects on gravity receptor function. 2018

Choongheon Lee, and Timothy A Jones
University of Nebraska-Lincoln, Department of Special Education and Communication Disorders, Lincoln, NE 68583-0738, USA. Electronic address: c.lee@wustl.edu.

Specific pharmacological blockade of KCNQ (Kv7) channels with XE991 rapidly (within 20 min) and profoundly alters inner ear gravity receptor responses to head motion (Lee et al., 2017). We hypothesized that these effects were attributable to the suppression of K+ secretion following blockade of KCNQ1-KCNE1 channels in vestibular dark cells and marginal cells. To test this hypothesis, K+ secretion was independently inhibited by blocking the Na+-K+-2Cl- cotransporter (NKCC1, Slc12a2) rather than KCNQ1-KCNE1 channels. Acute blockade of NKCC1 with ethacrynic acid (40 mg/kg) eliminated auditory responses (ABRs) within approximately 70 min of injection, but had no effect on vestibular gravity receptor function (VsEPs) over a period of 2 h in the same animals. These findings show that, vestibular gravity receptors are highly resistant to acute disruption of endolymph secretion unlike the auditory system. Based on this we argue that acute suppression of K+ secretion alone does not likely account for the rapid profound effects of XE991 on gravity receptors. Instead the effects of XE991 likely require additional action at KCNQ channels located within the sensory epithelium itself.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D004710 Endolymph The lymph fluid found in the membranous labyrinth of the ear. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Endolymphs
D004976 Ethacrynic Acid A compound that inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic. Edecrin,Etacrynic Acid,Ethacrinic Acid,Ethacrynate Sodium,Ethacrynic Acid, Sodium Salt,Hydromedin,Acid, Etacrynic,Acid, Ethacrinic,Acid, Ethacrynic,Sodium, Ethacrynate
D006112 Gravitation Acceleration produced by the mutual attraction of two masses, and of magnitude inversely proportional to the square of the distance between the two centers of mass. It is also the force imparted by the earth, moon, or a planet to an object near its surface. (From NASA Thesaurus, 1988) G Force,Gravistimulation,Gravity,Force, G,G Forces,Gravities
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000873 Anthracenes A group of compounds with three aromatic rings joined in linear arrangement.
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D014722 Vestibule, Labyrinth An oval, bony chamber of the inner ear, part of the bony labyrinth. It is continuous with bony COCHLEA anteriorly, and SEMICIRCULAR CANALS posteriorly. The vestibule contains two communicating sacs (utricle and saccule) of the balancing apparatus. The oval window on its lateral wall is occupied by the base of the STAPES of the MIDDLE EAR. Vestibular Apparatus,Ear Vestibule,Vestibular Labyrinth,Vestibule of Ear,Vestibulum Auris,Apparatus, Vestibular,Ear Vestibules,Labyrinth Vestibule,Labyrinth Vestibules,Labyrinth, Vestibular,Labyrinths, Vestibular,Vestibular Labyrinths,Vestibule, Ear,Vestibules, Ear,Vestibules, Labyrinth
D016057 Evoked Potentials, Auditory, Brain Stem Electrical waves in the CEREBRAL CORTEX generated by BRAIN STEM structures in response to auditory click stimuli. These are found to be abnormal in many patients with CEREBELLOPONTINE ANGLE lesions, MULTIPLE SCLEROSIS, or other DEMYELINATING DISEASES. Acoustic Evoked Brain Stem Potentials,Auditory Brain Stem Evoked Responses,Brain Stem Auditory Evoked Potentials,Evoked Responses, Auditory, Brain Stem,Acoustic Evoked Brain Stem Potential,Acoustic Evoked Brainstem Potential,Acoustic Evoked Brainstem Potentials,Auditory Brain Stem Evoked Response,Auditory Brain Stem Response,Auditory Brain Stem Responses,Auditory Brainstem Evoked Response,Auditory Brainstem Evoked Responses,Auditory Brainstem Responses,Brain Stem Auditory Evoked Potential,Brainstem Auditory Evoked Potential,Brainstem Auditory Evoked Potentials,Evoked Potential, Auditory, Brainstem,Evoked Potentials, Auditory, Brainstem,Evoked Response, Auditory, Brain Stem,Evoked Response, Auditory, Brainstem,Evoked Responses, Auditory, Brainstem,Auditory Brainstem Response,Brainstem Response, Auditory,Brainstem Responses, Auditory,Response, Auditory Brainstem,Responses, Auditory Brainstem

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