Canlon, B. & Brundin, L. Mechanically induced length changes of isolated outer hair cells are metabolically dependent. Hearing Res. 53, 7−16

Department of Physiology II, Karolinska Institute, Stockholm, Sweden.
Hearing Research (Impact Factor: 2.97). 06/1991; 53(1):7-16. DOI: 10.1016/0378-5955(91)90209-R
Source: PubMed


Isolated outer hair cells from the organ of Corti of the guinea pig have been shown to change length in response to a mechanical stimulus in the form of a tone burst at a fixed frequency of 200 Hz (Canlon et al., 1988). In the present study, the threshold of movement for individual outer hair cells is related to the original length of the cell such that long cells are more sensitive than short cells for all cochlear locations studied. Length changes could be elicited when the stimulus was projected at any site along the longitudinal axis of the plasma membrane. Length changes were not elicited when the stereocilia were stimulated directly. These mechanically-induced length changes were found to be metabolically dependent. In the presence of either sodium cyanide or 2,4-dinitrophenol, the motile response of outer hair cells was completely blocked within 30 min. When the extracellular pH was altered in a graded fashion, the motile response decreased gradually. Furthermore, 3 microM poly-L-lysine or poly-D-lysine of different molecular weights were also effective in blocking the motile response, whereas the negatively charged polyaminoacid, poly-L-aspartate, was not effective. Fluorescently-labelled poly-lysine demonstrated that the plasma membrane, stereocilia, and nucleus were the most intensely stained structures of the outer hair cells. It is suggested that the passive influx of poly-lysine is responsible for the inhibition of the motile response. Finally, the finding that the bidirectional motile response of isolated outer hair cells induced by mechanical stimulation is dependent on the metabolic state of the cell distinguishes this type of motility from the electrically induced outer hair cell shape changes.

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    • "The main effect of efferent stimulation is the physiologic alteration of outer hair cells (Ashmore, 1987; Canlon & Brudin, 1991). It is reported that efferent innervation of outer hair cells probably controls the cochlear amplifier , reduces the masking effects of noise, and protects the cochlea from the negative effects of acoustic over stimulation (Geisler, 1974; Kumar & Barman, 2002; Rajan, 1995; Wiederhold & Kiang, 1970). "
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    ABSTRACT: The purpose of the present study was to evaluate the relationship be-tween (1) the duration of contralateral acoustic stimulus and the sup-pression of transient evoked otoacoustic emissions (TEOAEs), and (2) the baseline TEOAE amplitude and the degree of TEOAE suppression. TEOAE amplitudes were measured in 50 normal hearing individuals in four con-ditions: once without any noise (baseline measurement); a second time after exposure to noise for 1 minute; a third time after 6 minutes of expo-sure to noise, and a fourth time, after exposure to noise for 11 minutes. Broadband noise was presented always to the contralateral ear at 50 dB SL. Results revealed a significant reduction in the magnitude of OAEs when noise was introduced. Magnitude of suppression reduced when broad-band noise was continued to 6 minutes. There was no relationship be-tween baseline amplitude of TEOAE and the degree of suppression. These
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    • "Via the N-terminal region of p 4.1 or ankyrin (Conboy, 1993; Tanner, 1993), this cytoskeletal network (cortical lattice) may be reversibly connected to transmembrane b3p located in the lateral OHCs membrane (Fig. 8). Chemical stimuli which induce actin-dependent length changes in OHCs (Zenner, 1986; Zenner, 1988; Slepecky et al., 1988; Canlon and Brundin, 1991; Slepecky and Ulfendahl, 1992) might then act via second messenger cascades to modify the p 4.1 or ankyrin anchor proteins or the integral b3p, thus controlling the interaction between the cortical lattice and the lateral membrane. Based on the mechanisms proposed for regulating RBC-shape changes, the modification of the key proteins involved in this type of OHC motility could be achieved by phosphorylation of specific sites mediated by tyrosine kinase (Yannoukakos et al., 1991), protein kinase A (Subrahmanyam et al., 1991), protein kinase C (Ling et al., 1988; Gascard et al., 1993), casein kinase I (Lu et al., 1985; Soong et al., 1987) or via binding of calmodulin to a specific domain of the p 4.1 (Chao and Tao, 1991; Conboy, 1993) or binding of Ca z+ to a specific site of the integral b3p (Salhany, 1990). "
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    ABSTRACT: By employing immunological methods, it has been demonstrated that myosin, myosin light chain (MLC) and myosin light chain kinase (MLCK) proteins in outer hair cells (OHC) are immunologically different from isoforms in platelets, smooth muscle and heart muscle, and are probably more related to isoforms found in red blood cells (RBC). Moreover, proteins related to band 3 protein (b3p) and protein 4.1 (p 4.1), ankyrin as well as fodrin and spectrin, but not glycophorin, have been identified in isolated OHCs. Both OHCs and RBC differ from other motile non-muscle cells in their lack of smooth muscle isoforms of actin, their common high levels of spectrin-, ankyrin- and band 3-like proteins, as well as the expression of the 80 kDa protein 4.1 isoform. The data support the notion that motility of OHC may be based upon regulation of the b3p/p 4.1/ankyrin complex, and thus may be reminiscent to the active shape changes in RBC.
    Full-text · Article · Jul 1995 · Hearing Research
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    ABSTRACT: Die Ätiologie des Hörsturzes ist weiterhin unbekannt und wird kontrovers diskutiert. In der vorliegenden Studie wurde die Mikrozirkulation, insbesondere die Verformbarkeit der Erythrozyten untersucht. Andere Parameter der Mirkozirkulation, wie die Thrombozytenaggregation und die Plasmaviskosität wurden ebenso diskutiert. Material und Methode 56 Hörsturzpatienten wurden mit einer rheologischen Infusionstherapie mit Pentoxifyllin (PTX) und 33 von Ihnen zusätzlich mit Prednisolon behandelt. Die gemessenen Mikrozirkulationsparameter wurden mit denen von 23 gesunden Probanden ohne bekannte Hörstörung verglichen. Zur Bestimmung der Erythrozytenverformbarkeit (EV) wurde das Laserdiffraktoskop angewandt. Mit dem 'Platelet function analyzer' wurde die Thrombozytenaggregation bestimmt. Wir verglichen Vollblutproben der Hörsturzpatienten (n=56; mittlerer Hörverlust 34 dB) vor der Therapie mit Vollblutproben der Kontrollgruppe, welche die gleiche Alters- und Geschlechtsverteilung aufwies. Die Blutproben der Patienten wurden am 1., 3. und 6. Tag der Therapie mit PTX, jeweils vor und nach der i.v.-Applikation den Messungen zugeführt. Zusätzlich wurden Blutproben von 9 Patienten nach einer Inkubation mit PTX in 10, 50 und 100facher Dosierung den Messungen zugeführt. Ergebnisse Die EV der Patientengruppe war bei physiologischen Scherkräften signifikant niedriger als die der Kontrollgruppe (p<0,05). PTX hat sowohl in vivo, als auch in vitro keinen positiven Effekt auf die EV bei physiologischen Scherkräften.Vor Beginn der Therapie war die Thrombozytenaggregation der Patienten im Vergleich zur Kontrollgruppe nicht erhöht, aber unter dem Einfluss der PTX-Infusionen nahm die Thrombozytenaggregation deutlich zu. Diese Ergebnisse wurden sowohl bei Patienten mit, als auch ohne Hörverbesserung gefunden. Der Plasmafibrinogenspiegel als Hinweis auf die Plasmaviskosität war vor der Therapie erhöht, wurde jedoch durch die Therapie reduziert und näherte sich dem Wert der Kontrollgruppe an. Diskussion Die EV ist eine der bedeutenden Parametern der Mikrozirkulation. Die Kapillaren haben einen kleineren Durchmesser als die Erythrozyten, so dass diese sich zur Passage der Kapillaren verformen müssen. Eine erniedrigte EV geht mit einer gesteigerten Viskosität und somit einer erniedrigten Mikrozirkulation einher. Bezüglich der Ergebnisse der hier vorliegenden Studie scheint eine verminderte EV an der Ätiologie der Hörsturzes beteiligt zu sein, PTX vermag die erniedrigte EV aber nicht positiv zu beeinflussen. Die Thrombozytenaggregation nahm während der Therapie zu, der Plasmafibrinogenspiegel sank. Die EV ist kein Prognosefaktor für den Schweregrad eines Hörsturzes oder den Therapieerfolg. Eine erhöhte Thrombozytenaggregation steht nicht im Zusammenhang mit dem Hörsturzereignis. Therapiealternativen wie die i.v.-Applikation von Mg++, welche die EV positiv beeinflussen soll, sowie die H.E.L.P.-Therapie sollten in Zukunft klinisch erprobt werden. The etiology of sudden sensorineural hearing loss is still in discussion. In our study we focused on microcirculation disorder especially on the red blood cell (RBC) flexibility. In addition to that, other parameters of the microcirculation like platelet aggregability and plasma viscosity were also discussed. Material and Method 56 patients were treated with a rheologic intravenous infusion therapy with pentoxifylline (PTX) and 33 of them additionally with prednisolone. The microcirculatory parameters were compared to the parameters of 23 healthy persons without hearing impairment. To examine the RBC flexibility we used the laserdiffractosope.We used the platelet function analyzer to test the platelet aggregability. We compared whole blood samples of patients suffering of sudden hearing loss (n=56 / average hearing loss 34 dB) prior to treatment with samples of a control group of matching age and sex. The blood samples of the patient group were measured on the 1st, 3rd and 6th day of treatment with PTX, before and directly after i.v. application. Additionally we measured blood samples of the patients (n=9) after in vitro incubation with PTX. Therefore we used dosages 10, 50 and 100 times as high as the therapeutic dose. Results The patient group showed under physiological shear stress a significant lower RBC flexibility than the control group (p<0,05). PTX had no significant influence on the RBC flexibility under physiological shear stress, both in vivo and in vitro. Before therapy started, the platelet aggregability of the patient group was not increased, but by the application of PTX it increased compared to the control group. This was found in patients with hearing recovery as well as without hearing recovery. The level of plasmafibrinogen as an indicator for the plasma viscosity was increased before therapy and decreased during therapy. Discussion Red blood cell flexibility is one of the determining parameters of microcirculation. As capillaries are less in diameter than RBC, RBC can only pass trough by reducing their diameter by deformation. Reduced flexibility is associated with an increased viscosity and a reduced microcirculation. Due to the results of our study, reduced RBC flexibility seems to be involved in the etiology of sudden deafness, but PTX did not improve RBC flexibility. Platelet aggregability raised during therapy, plasmafibrinogen decreased. RBC flexibility does not seem to be an indicator for recovery prognosis or recovery chances. Enhanced platelet aggregability has no impact on etiology of sudden sensorineural hearing loss. Therapeutic alternatives, for example the intravenous application of high dose Mg++, which has been shown recently to have a positive effect on RBC flexibility, or the H.E.L.P. therapy for reducing the plasmafibrinogen level, should be examined clinically and experimentally.
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