Mice lacking of voltage-gated L-type calcium channel alpha1D subunit have impaired sinoatrial node function and caused deafness.
- Author:
Hanqi CHU
1
,
2
;
Xiaoqin ZHOU
;
Haitao SONG
;
Yonghua CUI
;
Hao XIONG
;
Liangqiang ZHOU
Author Information
1. Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. qi7chu@
2. com
- Publication Type:Journal Article
- MeSH:
Animals;
Auditory Threshold;
Calcium Channels, L-Type;
genetics;
Deafness;
genetics;
physiopathology;
Electrocardiography;
Evoked Potentials, Auditory, Brain Stem;
Mice;
Mice, Knockout;
Sinoatrial Node;
physiopathology
- From:
Journal of Clinical Otorhinolaryngology Head and Neck Surgery
2007;21(10):468-472
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:L-type voltage-gated calcium channel subunit alpha1D-/- mice (homozygous mutant, knockout), alpha1D+/- (heterozygous) and alpha1D+/+ (wild-type) have played role in L-type voltage-gated calcium channel alpha1D subunit in auditory function of inner ear as well as sinoatrial node function of the mice.
METHOD:Hearing threshold and endocochlear potential (EP) were measured in the alpha1D knockout mice, heterozygous mice and wild-type mice by auditory brainstem response(ABR), EP recordings and Electrocardiograph (ECG) respectively. To assessment of the vestibular function of the mice, the ability of Balancing was performed by a swim test and a horizontal cylinder test.
RESULT:The auditory function of alD+/+ mice were normal, the mean value for ABR thresholds in response to click sound stimulus was (34.8 +/- 5.7) dB SPL,EP was (105.3 +/- 3.1) mV. The mean value for ABR thresholds in response to click sound stimulus was elevated in alpha1D+/- mice was (54.4 +/- 12.4) dB SPL, relative to that observed in alpha1D+/+ mice significantly increased (P < 0.05); EP of alpha1D+/- mice was about (75.8 +/- 9.9) mV. alpha1D-/- mice were completely deaf, the ABR wave form was not observed for even 100 dB SPL sound stimuli used and EP was still remain in (48.6 +/- 19.3) mV. alpha1D knockout mice were deaf and demonstrated no vestibular defect. alpha1D+/- and alpha1D-/- mice show significant sinus bradycardia with significant prolongation of the RR interval (146 +/- 1.4 and 244 +/- 2.9, respectively) comparing to the alpha1D+/+ wild-type mice (117 +/- 0.4) in the same littermates. In addition, the homozygous alpha1D-/- show a significant prolongation of the PR interval (53 +/- 0.5) compared to that of the a1D+/+ wild-type mice (38 +/- 0.3).
CONCLUSION:L-type voltage-gated calcium channel alpha1D subunit plays a critical role in calcium homeostasis in the inner ear. Mice lacking of alpha1D calcium channel gene would lead to influence auditory function and sinoatrial node dysfunction subsequently.
