Adenosine Triphosphate (ATP) Inhibits Voltage-Sensitive Potassium Currents in Isolated Hensen's Cells and Nifedipine Protects Against Noise-Induced Hearing Loss in Guinea Pigs.
BACKGROUND There is increasing evidence that adenosine triphosphate (ATP), a well-known neurotransmitter and neuromodulator in the central nervous system, plays an important role as an extracellular chemical messenger in the cochlea. MATERIAL AND METHODS Using a whole-cell recording technique, we studied the effects of ATP on isolated Hensen's cells, which are supporting cells in the cochlea, to determine if they are involved in the transduction of ions with hair cells. RESULTS ATP (0.1-10 µM) reduced the potassium current (IK+) in the majority of the recorded Hensen's cells (21 out of 25 cells). An inward current was also induced by high concentrations of ATP (100 µM to 10 mM), which was reversibly blocked by 100 µM suramin (a purinergic antagonist) and blocked by nifedipine (an L-type calcium channel blocker). After the cochleas were perfused with artificial perilymph solutions containing nifedipine and exposed to noise, the amplitude increase in the compound action potential (CAP) threshold and the reduction in cochlear microphonics was lower than when they were exposed to noise alone. CONCLUSIONS Our results suggest that ATP can block IK+ channels at a low concentration and induce an inward Ca2+ current at high concentrations, which is reversed by purinergic receptors. Nifedipine may have a partially protective effect on noise-induced hearing loss (NIHL).
Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China (mainland).
Rui
R
Ye
Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China (mainland).
Jun
J
Liu
, Xinjiang Cancer Hospital, Urumqi, Xinjiang, China (mainland).
Zhiying
Z
Jia
Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China (mainland).
Hongyang
H
Wang
, Academy of Military Medical Sciences, Beijing, China (mainland).
YongAn
Y
Wang
Center for Hearing & Deafness, State University of New York (SUNY) at Buffalo, Buffalo, NY, American Samoa.
Wei
W
Sun
Department of Radiation Oncology, Hainan Branch of Chinese PLA General Hospital, Sanya, Hainan, China (mainland).
Xuan
X
Wu
Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China (mainland).
Zhifei
Z
Zhao
Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China (mainland).
Baolong
B
Niu
Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China (mainland).
Xingqi
X
Li
Department of Oncology, Chinese PLA General Hospital, Beijing, China (mainland).
Guanghai
G
Dai
Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China (mainland).
Jianxiong
J
Li
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism / Q000517:prevention & control*; D009543:Nifedipine / Q000494:pharmacology*; D009925:Organ of Corti; D018408:Patch-Clamp Techniques / Q000379:methods; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011897:Random Allocation; D015398:Signal Transduction / Q000502:physiology; D013498:Suramin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D013498:Suramin; D000255:Adenosine Triphosphate; D009543:Nifedipine; D002118:Calcium