Wilson R I, Kunos G, Nicoll R A
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 94143, USA.
Neuron. 2001 Aug 16;31(3):453-62. doi: 10.1016/s0896-6273(01)00372-5.
Endocannabinoids are retrograde messengers released by neurons to modulate the strength of their synaptic inputs. Endocannabinoids are thought to mediate the suppression of GABA release that follows depolarization of a hippocampal CA1 pyramidal neuron-termed "depolarization-induced suppression of inhibition" (DSI). Here, we report that DSI is absent in mice which lack cannabinoid receptor-1 (CB1). Pharmacological and kinetic evidence suggests that CB1 activation inhibits presynaptic Ca2+ channels through direct G protein inhibition. Paired recordings show that endocannabinoids selectively inhibit a subclass of synapses distinguished by their fast kinetics and large unitary conductance. Furthermore, cannabinoid-sensitive inputs are unusual among central nervous system synapses in that they use N- but not P/Q-type Ca2+ channels for neurotransmitter release. These results indicate that endocannabinoids are highly selective, rapid modulators of hippocampal inhibition.
内源性大麻素是由神经元释放的逆行信使，用于调节其突触输入的强度。内源性大麻素被认为介导了海马CA1锥体神经元去极化后GABA释放的抑制，这一现象被称为“去极化诱导的抑制抑制”（DSI）。在此，我们报告在缺乏大麻素受体-1（CB1）的小鼠中不存在DSI。药理学和动力学证据表明，CB1激活通过直接抑制G蛋白来抑制突触前Ca2+通道。配对记录显示，内源性大麻素选择性抑制一类以快速动力学和大单位电导为特征的突触。此外，大麻素敏感的输入在中枢神经系统突触中是不寻常的，因为它们使用N型而非P/Q型Ca2+通道进行神经递质释放。这些结果表明，内源性大麻素是海马抑制的高度选择性、快速调节剂。
