A DIRECT EFFECT OF CALCIUM-ANTAGONISTS IN THE INNER-EAR - BLOCKAGE OFABNORMAL CALCIUM INCREASE IN OUTER HAIR-CELLS OF THE GUINEA-PIG

Calcium is considered to be a second messenger after the transduction process in outer hair cells and is needed in combination with actin an d myosin for slow cell motility. In analogy to the myocardium, abnorma l increases in intracellular (Ca2+) are believed to lead to cell death by the activation of calcium-sensitive proteases and phospholipases. Calcium overloading can be created by a high extracellular potassium m edium. In the present study we incubated isolated outer hair cells fro m the guinea pig in Hank's medium with and without the calcium channel antagonists verapamil chloride, flunarizin and nifedipine in concentr ations from 10(-9) M to 10(-4) M. We measured a calcium increase using the (FURA-2) method after an increase in extracellular potassium. In the same experiment we also measured the survival time of isolated out er hair cells. The results showed that calcium increases could be redu ced significantly in the presence of calcium antagonists. We also show ed that survival time could be significantly prolonged. Our conclusion s are that a protective effect of the calcium channel blockers exists for outer hair cells, and this effect is probably due to the presence of voltage-sensitive calcium channels of the L-type in the cell membra ne.