[Direct evidence of a protective effect of calcium antagonists on the inner ear. Inhibition of a toxic increase in the calcium level in 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 and myosin for slow cell motility. In analogy to the myocardium, abnormal 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 medium. In the present study we incubated isolated outer hair cells from the guinea pig in Hank's medium with and without the calcium channel antagonists verapamil chloride, flunarizin and nifedipine in concentrations 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 outer hair cells. The results showed that calcium increases could be reduced significantly in the presence of calcium antagonists. We also showed that survival time could be significantly prolonged. Our conclusions 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 membrane.
Nilles
R
R
Universitäts-HNO-Klinik Tübingen.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D005444:Flunarizine / Q000494:pharmacology; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000502:physiology; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014700:Verapamil; D009543:Nifedipine; D005444:Flunarizine; D011188:Potassium; D002118:Calcium