Wu Zi-Zhen, Pan Hui-Lin
Department of Anesthesiology, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Neurosci Lett. 2004 Sep 16;368(1):96-101. doi: 10.1016/j.neulet.2004.06.067.
Voltage-gated Ca(2+) channels in the primary sensory neurons are important for neurotransmitter release and regulation of nociceptive transmission. Although multiple classes of Ca(2+) channels are expressed in the dorsal root ganglion (DRG) neurons, little is known about the difference in the specific channel subtypes among the different types of DRG neurons. In this study, we determined the possible difference in high voltage-activated Ca(2+) channel currents between isolectin B(4) (IB(4))-positive and IB(4)-negative small-sized (15-30 microm) DRG neurons. Rat DRG neurons were acutely isolated and labeled with IB(4) conjugated to a fluorescent dye. Whole-cell patch clamp recordings of barium currents flowing through calcium channels were performed on neurons with and without IB(4). The peak current density of voltage-gated Ca(2+) currents was not significantly different between IB(4)-positive and IB(4)-negative neurons. Also, both nimodipine and omega-agatoxin IVA produced similar inhibitory effects on Ca(2+) currents in these two types of neurons. However, block of N-type Ca(2+) channels with omega-conotoxin GVIA produced a significantly greater reduction of Ca(2+) currents in IB(4)-positive than IB(4)-negative neurons. Furthermore, the IB(4)-positive neurons had a significantly smaller residual Ca(2+) currents than IB(4)-negative neurons. These data suggest that a higher density of N-type Ca(2+) channels is present in IB(4)-positive than IB(4)-negative small-sized DRG neurons. This differential expression of the subtypes of high voltage-activated Ca(2+) channels may contribute to the different function of these two classes of nociceptive neurons.
初级感觉神经元中的电压门控性Ca(2+)通道对于神经递质释放和伤害性感受传递的调节至关重要。尽管背根神经节(DRG)神经元中表达了多种类型的Ca(2+)通道,但对于不同类型DRG神经元中特定通道亚型的差异却知之甚少。在本研究中,我们确定了异凝集素B(4)(IB(4))阳性和IB(4)阴性的小型(15 - 30微米)DRG神经元之间高电压激活的Ca(2+)通道电流可能存在的差异。大鼠DRG神经元被急性分离并用与荧光染料偶联的IB(4)进行标记。对有或没有IB(4)的神经元进行了通过钙通道的钡电流的全细胞膜片钳记录。IB(4)阳性和IB(4)阴性神经元之间电压门控性Ca(2+)电流的峰值电流密度没有显著差异。此外,尼莫地平和ω-芋螺毒素IVA对这两种类型神经元的Ca(2+)电流产生了相似的抑制作用。然而,用ω-芋螺毒素GVIA阻断N型Ca(2+)通道后,IB(4)阳性神经元的Ca(2+)电流减少幅度明显大于IB(4)阴性神经元。此外,IB(4)阳性神经元的残余Ca(2+)电流明显小于IB(4)阴性神经元。这些数据表明,IB(4)阳性小型DRG神经元中N型Ca(2+)通道的密度高于IB(4)阴性小型DRG神经元。高电压激活的Ca(2+)通道亚型的这种差异表达可能有助于这两类伤害性感受神经元发挥不同的功能。