DISSOCIATION BETWEEN THE CALCIUM-INDUCED AND VOLTAGE-DRIVEN MOTILITY IN COCHLEAR OUTER HAIR-CELLS FROM THE WALTZING GUINEA-PIG

The waltzing guinea pig, possessing an hereditary progressive deafness , shows pathology to the actin-bearing structures within the hair cell s of the organ of Corti. In particular, the affected structures includ e the stereocilia, the cuticular plate and, as shown in the present st udy, swollen and disorganized subsurface cisternae. To test whether th is pathology affected outer hair cell motility, cells were isolated fr om waltzing guinea pigs and their age-matched controls and were subjec ted to either electrical or chemical stimulation. Visual detection thr esholds and the magnitude of the electrically-induced length changes w ere equivalent for both groups. However, when intracellular calcium wa s increased with either the calcium ionophore, ionomycin or Ca2+/ATP ( under permeabilized conditions with DMSO), length changes were signifi cantly reduced for the outer hair cells from waltzing guinea pigs comp ared to the controls. The average percent length increase induced by 1 0 muM ionomycin for the outer hair cells from control animals was 2.3 +/- 1.7 whereas for postnatal day 4 waltzing guinea pigs it was 1.3 +/ - 1.7. Postnatal day 7 and 10 waltzing guinea pigs responded with sign ificantly smaller percent length changes. The intracellular concentrat ion of ionic calcium increased similarly for both groups after the app lication of ionomycin as revealed with the indicator fluo-3. In the pe rmeabilized cells in the presence of Ca2+/ATP, control cells responded with a percent length change of 3.5, whereas, age-matched waltzing ou ter hair cells responded with barely detectable length changes. When t he osmolarity of the external medium was reduced, both the control and waltzing outer hair cells responded with a length change that was pro portional to the change in osmolarity, indicating the capability of pa ssive length changes. In summary, the voltage-dependent motility of is olated outer hair cells from the waltzing guinea pigs is intact, whils t the slow calcium-dependent motility is abnormal. As a result of thes e findings, the outer hair cells from the waltzing guinea pig allow se parations between the slow, metabolically dependent length changes ind uced by chemical stimulation and the fast, metabolically independent l ength changes induced by electrical stimulation.