Cisplatin induces calcium ion accumulation and hearing loss by causing functional alterations in calcium channels and...

In recent years, molecular biology and biochemistry have been a focus of studies on the ototoxic side effects of cisplatin. In this paper, the application of cisplatin for 4 h and 72 h was studied from the perspective of electrophysiological function. Patch clamp experiments and immunofluorescence staining were performed on inner hair cells of the cochlea. The patch-clamp results showed that the calcium current amplitude decreased significantly at 4 h and 72 h after cisplatin treatment, the reversal potential was negatively polarized, and the activation time decreased. We suspected that intracellular calcium accumulation was responsible for this result and confirmed this hypothesis by using calpain to measure intracellular calcium concentrations. We tested membrane capacitive function, whose levels after cisplatin application were significantly lower than those in the control group, thus indicating dysfunctional cytoplasmic effervescent function. CtBP2 staining was used to verify this result and indicated a decrease in ribbon synapses. Simultaneously, we observed dysfunction of vesicle circulation after cisplatin application. We found that cisplatin induces the accumulation of calcium ions in inner hair cells by calpain staining and fluoresce intensity calculation, thus decreasing calcium current and synaptic vesicle release, and impairing vesicles cycling, all of which are important mechanisms of cisplatin-induced hearing loss.