[Mice lacking of voltage-gated L-type calcium channel alpha1D subunit have impaired sinoatrial node function and caused deafness].
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Chu
Hanqi
H
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. qi7chu@163.com
Zhou
Xiaoqin
X
Song
Haitao
H
Cui
Yonghua
Y
Xiong
Hao
H
Zhou
Liangqiang
L
D000818:Animals; D001309:Auditory Threshold; D020746:Calcium Channels, L-Type / Q000235:genetics*; D003638:Deafness / Q000235:genetics* / Q000503:physiopathology*; D004562:Electrocardiography; D016057:Evoked Potentials, Auditory, Brain Stem; D051379:Mice; D018345:Mice, Knockout; D012849:Sinoatrial Node / Q000503:physiopathology*
C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type