毛细胞PMCA2在小鼠内耳Ca^(2+)调节和听觉平衡中的作用

Physiological function of plasma membrane Ca^(2+)-ATPase isoform 2 in inner ear hair cells of mouse

目的:研究小鼠内耳毛细胞细胞膜Ca2+-ATP酶2型蛋白(PMCA2)在听觉平衡生理中的作用及意义。方法:利用不同基因型小鼠PMCA2-/-(突变纯合子)、PMCA2+/-(杂合子)和PMCA2+/+(野生型)为实验对象,采用听觉脑干反应(ABR)、畸变产物耳声发射(DPOAE)和耳蜗内电位(EP)检测等方法,分别检测不同基因型小鼠的内耳生理功能。结果:PMCA2+/+野生型鼠的听力正常,ABR的短声(click)阈值为(13.75±11.08)dB SPL;EP均值为(91.3±11.0)mV。PMCA2+/-杂合子小鼠听力低于同窝PMCA2+/+野生型鼠,ABR的短声阈值为(63.89±12.90)dB SPL,与PMCA2+/+小鼠比较差异显著(P<0.01);PMCA2+/-小鼠没有检测出DPOAE的高频区辐值,其EP均值为(80.7±9.0)mV。PMCA2-/-小鼠的ABR在100dB SPL无反应,表现出全聋和平衡功能失调,其EP均值为(56.6±13.0)mV;PMCA2-/-小鼠没有检测出DPOAEs。结论:PMCA2是内耳毛细胞纤毛丛上的重要Ca2+转运通道,对维持内耳的Ca2+代谢和听觉平衡功能有重要作用。

AIM： To investigate the auditory and balanceable function of hair cell plasma membrane Ca^2＋ ATPase isoform 2 （PMCA2） channel in mouse inner ear. METHODS： Hearing threshold and endocochlear potential （EP） were measured in the PMCA2 homozygous mutants mice, heterozygous mice and wild -type mice by auditory brainstem response （ABR）, distortion product otoacoustic emission （DPOAE） and EP recordings, respectively. RESULTS： The auditory function in PMCA2 wild - type mice was normal, the mean value for ABR thresholds in response to click sound stimulus was （ 13.75 ± 11.08） dB SPL, EP was （91.3 ± 11.0） mV. The mean value for ABR thresholds in response to click sound stimulus was （63. 89 ± 12.90）dB SPL in PMCA2 heterozygous mice and significantly increased relative to that observed in PMCA2 wild - type mice （P 〈0.01 ）. EP in PMCA2 heterozygous mice was about （80. 7±9.0） mV and lower than that in PMCA2 wild- type mice but no statistics significance was observed （P 〉0. 05）. DPOAE thresholds increased and reduced amplitudes at high frequencies in PMCA2 heterozygous mice compared to wild - type mice. PMCA2 homozygous mutant mice were completely deaf, the ABR wave form was not observed even 100 dB SPL sound stimuli was used, the value of EP was （56.6 ± 13.0） mV lower than that in PMCA2 wild type mice （ P 〈 0. 05 ）. PMCA2 homozygous mutants mice did not produce DPOAEs, PMCA2 homozygous mutant mice were deaf and demonstrated difficulties in maintaining their balance. CONCLUSION： These data demonstrate that PMCA2 is required for both balance and hearing and suggest that it may be a major Ca^2＋ pump used in endolymph Ca^2＋ maintenance.