Kuniaki Takahashi

Nuclear transition of heat shock protein in guinea pig cochlea after hyperthermia.

The main reaction of heat shock protein (hsp) 70 family to heat shock is 2-fold, one is an increased synthesis in the cytoplasm and the other is a transition from the cytoplasm to the nucleus. Although the former has been already reported in the cochlea by several authors, there has been no description as to the latter. The present study was designed to determine whether this nuclear transition of hsp70 family is also present in the cochlea as in the other organs. Albino guinea pigs subjected to hyperthermia treatment (42 degrees C, 10 min) were killed at 0, 6, 18 or 24 h after the cessation of hyperthermia treatment. Immunohistochemical studies in the cochlea of the untreated animals revealed anti-hsp70 family immunoreactivity mainly in the cytoplasm of the various cells in the cochlea, including the interdental cells, the spiral ganglion cells or the outer hair cells. However, immunoreactivity remarkably increased in the nucleus immediately after the cessation of hyperthermia treatment and this increased immunoreactivity disappeared at 6 h or later. It is concluded that the nuclear transition of hsp70 family also takes place under hyperthermal stress in the cells of the cochlea as in other organs.

Very high levels of calmodulin (CAL) in outer hair cells (OHC) of organ of Corti (OC)

Using immunohistochemical techniques, Slepecky et al. [Hear. Res. 321, 11–22 (1988)] demonstrated a selective accumulation of CAL, an ubiquitous calcium binding protein, in the inner hair cells (IHC) and OHC of the OC. By quantitative polyacrylamide gel electrophoresis, it was found that in chinchilla OC, CAL is by far the highest in OHC, where levels of 6%–8% of total protein are reached. For comparison, the highest known accumulation of CAL (in the heads of spermatozoa) amounts to 12%. CAL is considerably lower in IHC (about 1%), and is not detectable with usual protein loads in other cell types of the OC. CAL is also very low in stria vascularis and Reissners membrane. The relative distribution of CAL in the OC is similar to that of glycogen, where the exceedingly high level of 600‐mmol/kg dry weight is reached in OHC [Thalmann et al., Laryngoscope 80, 1619–1645 (1970)]. This circumstantial evidence suggests that activation of phosphorylase kinase may be an important function of CAL in OHC, whereby ul...

Biochemical considerations in presbycusis

Virtually no direct information about biochemical changes in the peripheral auditory system due to aging is available. However, numerous predictions about biochemical changes due to characteristic degeneration patterns can be made indirectly. (1) Since glycogen and calmodulin are extremely high in outer hair cells, significant degeneration of these cells due to aging will result in lowered average levels of both substances in whole organ of Corti. Analogous considerations apply if major longitudinal gradients are present (e.g., glycogen, P‐creatine, cyclic GMP). (2) Degeneration of stria vascularis, the so‐called “metabolic” type of presbycusis, will result in a lowered endolymphatic potential and low endolymph K, while Na and Ca will be elevated. (3) The “inner ear conduction” type of presbycusis is associated with massive degeneration of the spiral ligament (SL). Apart from mechanical effects on basilar membrane motion, this should result in significant changes in perilymph chemistry. The normal SL exhibits extremely high carbonic anhydrase, which is thought to be essential in perilymph regulation. The SL also appears to be responsible for the markedly different kinetics of K and furosemide in scala vestibuli and tympani. The pronounced gradients of these substances between the scalae can no longer be maintained in the absence of a functional SL.Virtually no direct information about biochemical changes in the peripheral auditory system due to aging is available. However, numerous predictions about biochemical changes due to characteristic degeneration patterns can be made indirectly. (1) Since glycogen and calmodulin are extremely high in outer hair cells, significant degeneration of these cells due to aging will result in lowered average levels of both substances in whole organ of Corti. Analogous considerations apply if major longitudinal gradients are present (e.g., glycogen, P‐creatine, cyclic GMP). (2) Degeneration of stria vascularis, the so‐called “metabolic” type of presbycusis, will result in a lowered endolymphatic potential and low endolymph K, while Na and Ca will be elevated. (3) The “inner ear conduction” type of presbycusis is associated with massive degeneration of the spiral ligament (SL). Apart from mechanical effects on basilar membrane motion, this should result in significant changes in perilymph chemistry. The normal SL exhi...