Gopal Kamakshi V, Gross Guenter W
Department of Speech and Hearing Sciences, University of North Texas, Denton, TX 76203-5010, USA.
Hear Res. 2004 Jun;192(1-2):10-22. doi: 10.1016/j.heares.2004.01.016.
The anti-malarial drug quinine has several side effects including tinnitus. The aim of the study was to determine if cultured auditory networks growing on microelectrode arrays exhibited unique dynamic states when exposed to quinine. Eight auditory cortex networks (ACN), eight frontal cortex networks (FCN), and five inferior colliculus networks (ICN) were used in this study. Response of ACNs to quinine was biphasic, with an excitatory phase followed by inhibition. FCNs and ICNs revealed only inhibitory responses. The concentrations at which the spike rate was inhibited by 50% (IC50 mean +/- SE) were 42.5 +/- 3.9, 28.7 +/- 4.8 and 23.9 +/- 2.1 microM for ACNs, FCNs, and ICNs, respectively. Quinine increased the regularity and coordination of bursting in all three tissues. The increased burst pattern regularity of ICNs coupled with the excitatory responses seen only in ACNs between 1 and 10 microM show a unique susceptibility of auditory tissues to quinine that may be related to the underlying mechanism that triggers tinnitus-like activity.
抗疟药物奎宁有多种副作用,包括耳鸣。本研究的目的是确定生长在微电极阵列上的培养听觉网络在接触奎宁时是否表现出独特的动态状态。本研究使用了八个听觉皮层网络(ACN)、八个额叶皮层网络(FCN)和五个下丘网络(ICN)。ACN对奎宁的反应是双相的,先是兴奋期,然后是抑制期。FCN和ICN仅表现出抑制反应。ACN、FCN和ICN的 spike 率被抑制50%时的浓度(IC50平均值±标准误)分别为42.5±3.9、28.7±4.8和23.9±2.1微摩尔。奎宁增加了所有三种组织中爆发的规律性和协调性。ICN爆发模式规律性的增加,再加上仅在1至10微摩尔之间的ACN中观察到的兴奋反应,表明听觉组织对奎宁具有独特的敏感性,这可能与触发耳鸣样活动的潜在机制有关。