Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Berlin-Buch D-13092 Germany.
J Physiol. 2011 May 1;589(Pt 9):2229-43. doi: 10.1113/jphysiol.2010.203463. Epub 2011 Feb 28.
In mammals there are three types of low-voltage-activated (LVA) calcium channels,Cav3.1, Cav3.2 and Cav3.3, which all give rise to T-type Ca2+currents. T-type Ca2+currents have long been known to be highly enriched in a sub-population of medium-sized sensory neurones in the dorsal root ganglia (DRG). However, the identity of the T-type-rich sensory neurones has remained controversial and the precise physiological role of the Cav3.2 calcium channel in these sensory neurones has not been directly addressed. Here we show, using Cav3.2−/− mutant mice,that these channels are essential for the normal temporal coding of moving stimuli by specialized skin mechanoreceptors called D-hair receptors.We show that D-hair receptors from Cav3.2−/− fire approximately 50% fewer spikes in response to ramp-and-hold displacement stimuli compared to wild type receptors. The reduced sensitivity of D-hair receptors in Cav3.2−/− mice is chiefly due to an increase in the mechanical threshold and a substantial temporal delay in the onset of high-frequency firing to moving stimuli.We examined the receptive properties of other cutaneous mechano receptors and Aδ- and C-fibre nociceptors in Cav3.2−/− mice, but found no alteration in their mechanosensitivity compared to Cav3.2+/+mice. However, C-fibre nociceptors recorded in Cav3.2−/− mutant mice displayed a small but statistically significant reduction in their spiking rate during noxious heat ramps when compared to C-fibres in control mice. The T-type calcium channel Cav3.2 is thus not only a highly specific marker of D-hair receptors but is also required to maintain their high sensitivity and above all to ensure ultra rapid temporal detection of skin movement.
在哺乳动物中，有三种类型的低电压激活（LVA）钙通道，Cav3.1、Cav3.2 和 Cav3.3，它们都产生 T 型 Ca2+电流。T 型 Ca2+电流在背根神经节（DRG）中的一小部分中型感觉神经元中高度富集，这一点早已为人所知。然而，富含 T 型的感觉神经元的身份一直存在争议，Cav3.2 钙通道在这些感觉神经元中的精确生理作用尚未得到直接解决。在这里，我们使用 Cav3.2−/− 突变小鼠表明，这些通道对于专门的皮肤机械感受器（称为 D 毛感受器）对运动刺激的正常时间编码是必不可少的。我们发现，与野生型受体相比，Cav3.2−/− 小鼠的 D 毛感受器对斜坡和保持位移刺激的反应大约少发射 50%的尖峰。Cav3.2−/− 小鼠中 D 毛感受器的敏感性降低主要是由于机械阈值增加以及对运动刺激的高频发射起始的明显时间延迟。我们检查了 Cav3.2−/− 小鼠中其他皮肤机械感受器和 Aδ-和 C-纤维伤害感受器的感受特性，但与 Cav3.2+/+ 小鼠相比，它们的机械敏感性没有改变。然而，与对照小鼠相比，在 Cav3.2−/− 突变小鼠中记录的 C 纤维伤害感受器在受到有害热斜坡刺激时，其放电率略有但统计学上显著降低。因此，T 型钙通道 Cav3.2 不仅是 D 毛感受器的高度特异性标志物，而且对于维持其高灵敏度，尤其是确保对皮肤运动的超快速时间检测也是必需的。
