Potassium Concentration Of Endolymph Research Articles

Localization and functional studies of pendrin in the mouse inner ear provide insight about the etiology of deafness in pendred syndrome.

Immunolocalization studies of mouse cochlea and vestibular end-organ were performed to study the expression pattern of pendrin, the protein encoded by the Pendred syndrome gene (PDS), in the inner ear. The protein was restricted to the areas composed of specialized epithelial cells thought to play a key role in regulating the composition and resorption of endolymph. In the cochlea, pendrin was abundant in the apical membrane of cells in the spiral prominence and outer sulcus cells (along with their root processes). In the vestibular end-organ, pendrin was found in the transitional cells of the cristae ampullaris, utriculi, and sacculi as well as in the apical membrane of cells in the endolymphatic sac. Pds-knockout (Pds-/-) mice were found to lack pendrin immunoreactivity in all of these locations. Histological studies revealed that the stria vascularis in Pds-/- mice was only two-thirds the thickness seen in wild-type mice, with the strial marginal cells showing irregular shapes and sizes. Functional studies were also performed to examine the role of pendrin in endolymph homeostasis. Using double-barreled electrodes placed in both the cochlea and the utricle, the endocochlear potential and endolymph potassium concentration were measured in wild-type and Pds-/- mice. Consistent with the altered strial morphology, the endocochlear potential in Pds-/- mice was near zero and did not change during anoxia. On the other hand, the endolymphatic potassium concentration in Pds-/- mice was near normal in the cochlea and utricle. Together, these results suggest that pendrin serves a key role in the functioning of the basal and/or intermediate cells of the stria vascularis to maintain the endocochlear potential, but not in the potassium secretory function of the marginal cells.

A negative correlation between endocochlear potential and endolymph potassium concentration

It is widely accepted that the endocochlear potential (EP) arises from a secretion of K+ into endolymph by stria vascularis, although, as yet, there is no consensus concerning that cellular basis of this process. Studies in which changes in EP and endolymph potassium (Ke) were recorded during anoxia or treatment with transport inhibitors (e.g., ouabain) have shown that a decline of Ke is associated with the suppression of EP. On the basis of such experiments, it would be presumed that Ke would tend to be positively correlated with the magnitude of EP. On the contrary, a number of procedures have been found in which a decrease of Ke is associated with an increase of EP. Perilymphatic perfusion of solution containing 20 mM K+ caused a transient increase of EP (by up to 10 mV) followed by a decline. During this period, Ke recorded by ion‐selective microelectrodes typically showed a decrease, followed by an increase. Similarly, iontophoretic injection of Ca++ into endolymph produced an EP decrease that was mirrored by a Ke increase. These findings cannot be explained by changes in K+ transport and/or K+ permeability alone, but are more likely accounted for by changes in anion permeability. [Work supported by NIH Program Grant No. P01 NS24372.]

Ionic environment of cochlear hair cells.

The scala media of the adult cochlea in mammals comprises a morphologically closed compartment sealed with tight junctions of the intermediate to tight types. The unique ionic composition of endolymph is maintained by the stria vascularis through active reabsorption of sodium and active secretion of potassium against ionic gradients. The subtectorial space is only a partially closed compartment which communicates with the endolymph via holes in the tectorial membrane at its outer insertion to the organ of Corti. Hardesty's membrane divides the subtectorial space into two compartments: one facing the surfaces of inner hair cells and one facing the surfaces of outer hair cells. In the study of comparative anatomy, hair cells, e.g. in the lizard, basilar papilla are of two types: those covered with a tectorial membrane and those being free-standing lacking the tectorial membrane. The ionic environment of the hair cell surface seems to be the same, independent of whether covered with a tectorial membrane or not. The tectorial membrane itself is semipermeable to ions in the endolymphatic space. Only the surface structures of the hair cell with the sensory hairs facing the subtectorial space are exposed to the high concentration of potassium, whereas the remaining parts of the hair cell are surrounded by a fluid having a more normal extracellular type of ionic composition (cortilymph/perilymph). During embryonic development the ionic composition of endolymph develops in parallel with the morphologic maturation of the stria vascularis. A completely mature composition of endolymph is reached before any electrophysiological potentials in the cochlea can be elicited. The sensory hair surface of hair cells has reached a mature morphology prior to the maturation of endolymph. In several species the tectorial membrane is morphologically only partially mature when the increase of the potassium concentration of endolymph starts. Drugs primarily affecting the stria vascularis causing a transient change of the ionic composition of endolymph result in a transient dysfunction of inner ear potentials. If the ionic changes persist for longer time, morphological changes can occur in both the stria vascularis and the hair cells of the organ of Corti. Whether such changes are primarily caused by the ototoxic drug itself or by changes in the ionic composition of endolymph has to be explored further.

Furosemide ototoxicity: clinical and experimental aspects.

Furosemide is an ototoxic diuretic. Furosemide injection is followed by a rapid, but reversible decrease of the endocochlear potential and eighth nerve action potential with a more gradual decrease of the endolymph potassium concentration. In contrast to the reversible effects of furosemide alone on the cochlea, the combination of kanamycin with furosemide resulted in irreversible changes in cochlear function which were associated with elevated levels of kanamycin in the blood and perilymph of the experimental animals. There was a striking similarity between the blood level measured by high pressure liquid chromatography at the time of recovery of auditory function in experimental animals and the ototoxic blood levels proposed by others in clinical literature. These findings help to provide a pharmacologic basis for the clinical observation of furosemide-induced hearing loss.

Effect of furosemide upon endolymph potassium concentration.

Chinchillas were anesthetized with ketamine (40 mg/kg i.m.) and endocochlear potential (EP) and potassium concentration in endolymph (Ke+) were determined in control animals and in animals injected with various doses of furosemide (25, 50 or 100 mg/kg i.v.) by means of microelectrodes inserted into scala media. Control EP and Ke+ in the chinchilla were 81.3 +/- 3.8 mV and 158.5 +/- 3.2 mequiv./l, respectively. Following injection of furosemide, a dose-related fall in EP and Ke+ was observed. However, the EP declined much more rapidly than the Ke+, and recovered more quickly than the latter. The recovery of Ke+ tended to lag behind the EP recovery. The debate over whether potassium transport into endolymph and endocochlear potential generation are related or independent events is discussed in the light of recent literature and the present study.

Changes in EP and K+ in the inner ear fluids following loop diuretics

Pathogenesis of inner ear deafness are thought to be due largely to imbalance of potassium and sodium ions in the inner ear fluids. Such imbalance can occur with renal diseases, vascular insufficiencies, and ototoxic drugs. An ion-specific micro-electrode was applied to the peri- or endo-lymph in chinchilla's cochlea. Simultaneous measurements of endocochlear dc potentials (EP) and K-ion concentration were made over a period of a few hours and their changes following temporary asphyxia, following various loop diuretics, following permanent anoxia were studied. The reduction of endolymph potassium concentration was accompanied by the elevation of perilymph concentration of this cation following loop diuretics. Normal values for K+ in the inner ear fluids and potassium conductance following various doses of loop diuretics will be discussed in detail.

Effects of noise on cochlear potentials and endolymph potassium concentration recorded with potassium-selective electrodes

Guinea pig cochleas were exposed to either broad-band noise at intensities between 95 and 115 dBA or octave-band noise centered at 380 Hz or 4.2 kHz at intensities between 115 and 125 dB SPL. Cochlear microphonics (CM), summating potentials (SP) and action potentials (AP) were recorded from differential electrodes in the perilymphatic scalae between successive 20-min periods of noise exposure. The endocochlear potential (EP) and endolymph potassium concentration [K endo +] were recorded continuously from scala media using double-barreled potassium-sensitive electrodes. It was found that the initial exposure to noise at 115 dBA produced considerable supression of the CM and AP, while the EP and [K endo +] were elevated above their normal values. When animals previously treated with kanamycin were subjected to the same level of noise exposure no systematic increase in either EP or [K endo +] was observed. After prolonged exposure to 380 Hz octave-band noise at 125 dB SPL, a slow decline of EP and [K endo +] was observed. The relationships between the changes in EP, [K endo +] and CM are discussed.

Propranolol antagonism to the effect of furosemide on the compostion of endolymph in guinea pigs.

Furosemide, administered intravenously (50 mg/kg) to guinea pigs, caused an increase in the sodium concentration and a decrease in the potassium concentration of endolymph, and a fall in the endolymphatic potential. The furosemide-induced electrolyte changes were prevented by pretreatment of five guinea pigs with propranolol given intravenously (2 mg/kg). The fall in the endolymphatic potential was not prevented by propranolol. Local administration of furosemide to the perilymphatic or endolymphatic space caused a fall in the endolymphatic potential, but had no effect upon the concentrations os sodium and potassium of endolymph. These studies provide additional information suggesting the mutual independence of the endolymphatic potential and sodium and potassium concentration gradients.

Evidence for an electrogenic potassium pump as the origin of the positive component of the endocochlear potential.

The endocochlear potential (EP) and endolymph potassium concentration [K+] e were measured in the first turn of the guinea pig cochlea. Liquid ion exchanger K+ specific microelectrodes were used for [K+] measurement. The resting value of the cochlea endolymph [K+] e was 140±8.6 mM. The [K+] e was then reduced by perfusing scale media with K+ substituted Ringers containing 5, 20 or 50 mM K+. EP fell rapidly after perfusion to steady values of 9–35 mV and the [K+] e returned to stable values of 62–130 mM. The K+ conductance [G K] was calculated assuming that EP was produced by K+ current to be 0.16×10−7 mMoles/min/mV/mm of scala media. Active K+ flux was calculated from the measured flux after perfusion and the passive flux was derived fromG K and the driving force for K+. It was concluded that the assumption that EP is generated by K+ current is justified and that the electrogenic K+ flux after perfusion was accompanied by an apparently electroneutral flux.

Ethacrynic acid effect on the composition of cochlear fluids.

Ethacrynic acid, when administered to six dogs, caused a fall in the concentration of potassium in endolymph from 145 to 21 milliequivalents per liter and a rise in the concentration of sodium from 5.9 to 146 milliequivalents per liter. The composition of perilymph is unaffected. Perilymph and endolymph are slightly hypertonic as compared to plasma.

The ion selective function of the epithelium of the membranous canal walls.

Experiments on an isolated canal in the living animal have shown that blocking of the vascular supply results in a decrease in endolymph potassium concentration in this canal. In three hours of vascular blockade, the concentration falls to that of the surrounding perilymph. If the isolated canal has been filled with artificial perilymph and its vascular supply intact, the potassium concentration increases, indicating a selective ion-transport function of the canal epithelium which, under normal conditions, might contribute to maintaining the high potassium concentration of the endolymph in the canals as well as in the rest of the membranous labyrinth.