Calcium imaging in gentamicin ototoxicity: increased intracellular calcium relates to oxidative stress and late apoptosis.
OBJECTIVE
To estimate intracellular calcium changes in gentamicin (GM) ototoxicity using calcium imaging. To investigate GM-induced physiologic changes in auditory cells including cell viability, apoptosis, and oxidative stress.


METHODS
Varying concentrations of GM were applied to the HEI-OC1 cochlear cell line. Calcium imaging tracked changes in intracellular calcium concentration during GM cytotoxicity. Cell viability and intracellular reactive oxygen species (ROS) levels also were measured.


RESULTS
Little change in calcium levels occurred in HEI-OC1 cells exposed to less than 35 mM GM. However, calcium rose continuously in cells exposed to more than 60 mM GM. With administration of intermediate concentrations of 40 or 50 mM GM, calcium increased variably in different cells, returning to baseline in some cases, or rising continuously in others. Upon increase of GM concentration, intracellular calcium concentration and ROS were increased, and cell viability was decreased due to late apoptosis.


CONCLUSIONS
This study shows that GM increased intracellular calcium, ROS, and late apoptosis of HEI-OC1 cells derived from cochlear tissue. Increase of intracellular calcium is related to GM-induced apoptosis and oxidative stress. Calcium imaging can be used to determine change of intracellular calcium concentrations and apoptosis in GM ototoxicity.
Department of Otolaryngology-Head and Neck Surgery, Korea University College of Medicine, 126-1 Anam-dong 5-Ga, Seongbuk-Gu, Seoul 136-705, South Korea. brune77@naver.com
Jiwon
J
Chang
Ji Yun
JY
Yang
June
J
Choi
Hak Hyun
HH
Jung
Gi Jung
GJ
Im
D017209:Apoptosis; D002118:Calcium / Q000032:analysis*; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival; D003051:Cochlea / Q000166:cytology*; D005839:Gentamicins / Q000633:toxicity*; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000032:analysis
D005839:Gentamicins; D017382:Reactive Oxygen Species; D002118:Calcium