Proft Juliane, Weiss Norbert
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Mol Pharmacol. 2015 Jun;87(6):890-906. doi: 10.1124/mol.114.096008. Epub 2014 Dec 30.
Neuronal voltage-gated calcium channels have evolved as one of the most important players for calcium entry into presynaptic endings responsible for the release of neurotransmitters. In turn, and to fine-tune synaptic activity and neuronal communication, numerous neurotransmitters exert a potent negative feedback over the calcium signal provided by G protein-coupled receptors. This regulation pathway of physiologic importance is also extensively exploited for therapeutic purposes, for instance in the treatment of neuropathic pain by morphine and other μ-opioid receptor agonists. However, despite more than three decades of intensive research, important questions remain unsolved regarding the molecular and cellular mechanisms of direct G protein inhibition of voltage-gated calcium channels. In this study, we revisit this particular regulation and explore new considerations.
神经元电压门控钙通道已演变成负责神经递质释放的突触前终末中钙内流的最重要参与者之一。反过来，为了微调突触活动和神经元通讯，众多神经递质对G蛋白偶联受体提供的钙信号施加有力的负反馈。这条具有生理重要性的调节途径也被广泛用于治疗目的，例如吗啡和其他μ-阿片受体激动剂用于治疗神经性疼痛。然而，尽管经过三十多年的深入研究，关于G蛋白直接抑制电压门控钙通道的分子和细胞机制仍有重要问题未得到解决。在本研究中，我们重新审视这一特殊调节并探索新的思考。
