INHIBITION OF CALCIUM-DEPENDENT MOTILITY OF COCHLEAR OUTER HAIR-CELLSBY THE PROTEIN-KINASE INHIBITOR, ML-9

The calcium ionophore ionomycin has been shown to induce length increa ses of guinea pig outer hair cells (Dulon et al., 1990). We have demon strated that these length increases can be inhibited by a 30 min prein cubation of the cells with the protein kinase inhibitor ML-9. At eithe r 30 or 60 s after ionomycin application, the effect of ML-9 was dose- dependent with a half maximal response at approximately 0.3 mu M. No e ffect on cell length was detected after:30 min incubation with 0.5 and 5 mu M ML-9 alone. However, with 50 and 500 mu M ML-9, significant co ntraction in cell length was observed. 50 mu M ML-9 did not interfere with the ability of ionomycin to elevate fluorescence of the calcium i ndicator Fluo-3, nor did it after the ability of cells to exclude prop idium iodide from their nuclei. Treatment with 500 mu M ML-9 resulted in impaired cell morphology. The data support the hypothesis that prot ein kinase activity regulates calcium-dependent processes that effect shape changes of outer hair cells. They are consistent with the involv ement of the calcium/calmodulin-dependent enzyme, myosin light chain k inase, a known target of ML-9, but do not preclude the possibility of another intracellular target for ML-9. (C) 1998 Published by Elsevier Science B.V. All rights reserved.