Contribution of L-type Voltage Sensitive Ca^<2+> Channels to Mechanism of General Anesthesia

[体外]采用大鼠脑片K~(++)诱发的神经递质(去甲肾上腺素[NA]、多巴胺和谷氨酸)释放模型，研究静脉麻醉剂对电压敏感钙通道(VSCCs)的影响。首先，我们发现这种释放主要通过P/Q-VSCCs介导。第二，除氯胺酮外，静脉注射麻醉剂均以浓度依赖的方式显著抑制神经递质释放。因此，这些麻醉剂可以抑制VSCC，但GABA_A受体拮抗剂荷包牡丹碱能逆转静脉麻醉剂的抑制作用。因此，这些麻醉剂激活GABAA受体可能会降低VSCC的活性。[在活体]我们用微透析法研究了普通麻醉剂对几个脑区NA释放的影响。我们发现，抑制NMDA受体的麻醉剂增加了NA的释放，而激活GABA_A受体的麻醉剂则减少了这种释放。同时具有上述两种特性的异氟醚可减少大脑皮层的释药，增加下丘脑前部视前区的释药。由于睡眠诱导的NA能神经元的存在，NMDA拮抗剂类麻醉剂增加NA的释放可能有助于激活睡眠诱导的NA能神经元。相反，GABA_A激动剂类麻醉剂减少NA的释放可能导致觉醒诱导的NA能神经元受到抑制。

[In Vitro] We used model of K^+-evoked neurotransmitter (noradrebaline [NA], dopamine and glutamate) release from rat brain slices to study effects of iv anesthetic agents on voltage sensitive Ca^<2+> channels (VSCCs). First, we found that the release is mediated mainly via P/Q-VSCCs. Second, iv anesthetic agents except ketamine significantly inhibit the release in a concentration dependent manner. Thus, these anesthetic agents may inhibit VSCC.However, bicuculline, a GABA_A receptor antagonist, reversed the inhibitory effects of iv anesthetic agents. Therefore, it is likely that activation of GABA_A receptors by these anesthetic agents may reduce VSCC activities.[In Vivo] Using microdialysis method, we studied effects general anesthetic agents on NA release from several brain regions. We found that anesthetics inhibiting NMDA receptor increase NA release, whereas anesthetics activating GABA_A receptor reduce the release. Isoflurane that has both characters decreases the release in the cerebrocortex and increases in the preoptic area of anterior hypothalamus. As sleep-inducing NAergic neurons exist, increase in NA release by NMDA antagonist like anesthetics may contribute to activating sleep-inducing NAergic neurons. In contrast, decrease in NA release by GABA_A agonist like anesthetics may induces inhibition of wakefulness-inducing NAergic neurons.