Implications of cellular models of dopamine neurons for schizophrenia.
Implications of cellular models of dopamine neurons for schizophrenia.
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DOI：
10.1016/b978-0-12-397897-4.00011-5
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发表时间：
2014
影响因子：
--
通讯作者：
Canavier, Carmen C.
中科院分区：
文献类型：
--
作者：
Yu, Na;Tucker, Kristal R.;Levitan, Edwin S.;Shepard, Paul D.;Canavier, Carmen C.
中脑多巴胺神经元在体外是起搏器，但在体内，它们的放电不太规律，偶尔会爆发，导致去极化阻滞产生的放电暂时停止。用于治疗精神分裂症阳性症状的抗精神病药物的治疗效果归因于它们在亚群多巴胺神经元内诱导去极化阻滞的能力。我们总结了实验的结果，这些神经元的能力，在体外进入去极化块的生理机制，以及我们的这些实验的计算机模拟。我们认为，电压依赖性Na+通道的失活，特别是这种失活的较慢的组成部分，在控制进入去极化阻滞是至关重要的。此外，一个醚-a-go-相关基因（ERG）的K+电流似乎也参与延迟进入和加速从去极化阻滞恢复。由于许多抗精神病药物都具有阻断这种电流的能力，因此ERG通道可能有助于这些药物的治疗效果。
Midbrain dopamine neurons are pacemakers in vitro, but in vivo they fire less regularly and occasionally in bursts that can lead to a temporary cessation in firing produced by depolarization block. The therapeutic efficacy of antipsychotic drugs used to treat the positive symptoms of schizophrenia has been attributed to their ability to induce depolarization block within a subpopulation dopamine neurons. We summarize the results of experiments characterizing the physiological mechanisms underlying the ability of these neurons to enter depolarization block in vitro, and our computational simulations of those experiments. We suggest that the inactivation of voltage-dependent Na+ channels, and in particular the slower component of this inactivation, is critical in controlling entry into depolarization block. In addition, an ether-a-go-related gene (ERG) K+ current also appears to be involved by delaying entry into and speeding recovery from depolarization block. Since many antipsychotic drugs share the ability to block this current, ERG channels may contribute to the therapeutic effects of these drugs.