Vizi E S
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Neurochem Int. 1998 Oct;33(4):359-66. doi: 10.1016/s0197-0186(98)00040-0.
The temperature dependence of transmitter release associated with axonal conduction, evoked by ligand-gated mechanism and by reversed operation of plasma membrane transporter was studied in superfused slice preparation. When the temperature was reduced from 37-17 degrees C the release of [3H]noradrenaline ([3H]NA) and [3H]dopamine ([3H]DA) in response to field stimulation was significantly enhanced in slice preparations of the hippocampus and main olfactory bulbs. The release of [3H]dopamine evoked by a ligand-gated mechanism (nicotine receptor stimulation) was potentiated at low temperature (12 degrees C). In contrast, when transmitter release was evoked by ouabain, a drug inhibiting Na+/K+-activated ATPase and thereby increasing [Na+]i the release of [3H]GABA was enhanced. This release was very sensitive to cooling (Q10=3.5 between 37 degrees C and 27 degrees C), indicating that the release was induced by a reversed operation of the transporter. The excessive release of [3H]NA from the hippocampal slice in response to oxygen and glucose deprivation (simulation of ischemia) was also inhibited in a temperature-dependent manner. Because at low temperatures (17-12 degrees C) only one type of release mechanism (exocytosis) is operational and carrier-mediated uptake and release is inhibited, this temperature condition provides a method to study the mode of action of different drugs (e.g. amphetamine) and the effect(s) of certain conditions (e.g. ischemia) on the mechanisms of transmitter release, specifically whether they exert their transmitter releasing effect through an exocytotic process or through the reversed operation of plasma membrane transporter. This finding also suggests that it would be important to re-examine mechanistic conclusions based on results from electrophysiological, neurochemical and pharmacological studies that have been carried out at room temperature (approximately 20 degrees C). In particular because transmitter release associated with the action potential, diffusion, receptor kinetics, active transport in both directions (uptake and release) and the probability of transmitter release are all temperature dependent, it would seem important to carry out experiments involving these processes at physiological temperature (37 degrees C).
在灌流脑片制备中，研究了与轴突传导相关的递质释放的温度依赖性，该释放由配体门控机制和质膜转运体的反向运作所引发。当温度从37℃降至17℃时，海马体和主嗅球脑片标本中，响应场刺激的[3H]去甲肾上腺素（[3H]NA）和[3H]多巴胺（[3H]DA）释放显著增强。由配体门控机制（尼古丁受体刺激）引发的[3H]多巴胺释放在低温（12℃）下增强。相反，当哇巴因引发递质释放时，哇巴因是一种抑制Na+/K+激活的ATP酶从而增加细胞内[Na+]的药物，[3H]GABA的释放增强。这种释放在冷却时非常敏感（37℃至27℃之间Q10 = 3.5），表明该释放是由转运体的反向运作诱导的。海马体脑片中[3H]NA因缺氧和葡萄糖剥夺（模拟缺血）而导致的过度释放也以温度依赖的方式受到抑制。因为在低温（17℃至12℃）下只有一种释放机制（胞吐作用）起作用，且载体介导的摄取和释放受到抑制，这种温度条件提供了一种方法来研究不同药物（如苯丙胺）的作用方式以及某些条件（如缺血）对递质释放机制的影响，特别是它们是通过胞吐过程还是通过质膜转运体的反向运作发挥其递质释放作用。这一发现还表明，重新审视基于在室温（约20℃）下进行的电生理、神经化学和药理学研究结果得出的机制性结论很重要。特别是因为与动作电位、扩散、受体动力学、双向主动转运（摄取和释放）以及递质释放概率相关的递质释放都依赖于温度，在生理温度（37℃）下进行涉及这些过程的实验似乎很重要。
