R-type Calcium Channel Isoform in Rat Dorsal Root Ganglion Neurons
R-type Calcium Channel Isoform in Rat Dorsal Root Ganglion Neurons
复制标题
DOI：
10.4196/kjpp.2010.14.1.45
复制
发表时间：
2010-02-01
影响因子：
2
通讯作者：
Oh, Seog Bae
中科院分区：
文献类型：
--
作者：
Fang, Zhi;Hwang, Jae Hong;Oh, Seog Bae
外周感觉神经元R-型钙(V)2.3高电压激活的钙通道参与痛觉传递。最近我们发现，在六种Ca(V)2.3亚型(类似于Ca(V)2.3e)中，Ca(V)2.3e亚型主要表达于三叉神经节(TG)伤害性神经元。在本研究中，我们进一步研究了Ca(V)2.3亚型在背根节(DRG)神经元中的表达模式。与TG神经元一样，全组织RT-PCR分析表明，在DRG神经元中存在两种异构体，即Ca(V)2.3a和Ca(V)2.3e。单细胞RT-PCR检测到20%(n=14/70)的DRG神经元表达Ca(V)2.3e，而2.8%(n=2/70)的DRG神经元表达Ca(V)2.3a。Ca(V)2.3E mRNA主要在小型神经元中表达(n=12/14)，在少数中型神经元中表达(n=2/14)，而在大型神经元中不表达，表明Ca(V)2.3E在伤害性感受性背根节神经元中显著表达。此外，Ca(V)2.3E在酪氨酸激酶A(TrkA)阳性、异凝集素B4(IB4)阴性和瞬时受体电位香草素1(TRPV1)阳性神经元中优先表达。这些结果表明，Ca(V)2.3e可能是伤害性DRG神经元中主要的R型钙通道亚型，因此不仅在三叉神经系统，而且在脊髓系统，Ca(V)2.3e可能是治疗疼痛的潜在靶点。
R-type Ca(v)2.3 high voltage-activated Ca2+ channels in peripheral sensory neurons contribute to pain transmission. Recently we have demonstrated that, among the six Ca(v)2.3 isoforms (Ca(v)2.3a similar to Ca(v)2.3e), the Ca(v)2.3e isoform is primarily expressed in trigeminal ganglion (TG) nociceptive neurons. In the present study, we further investigated expression patterns of Ca(v)2.3 isoforms in the dorsal root ganglion (DRG) neurons. As in TG neurons, whole tissue RT-PCR analyses revealed the presence of two isoforms, Ca(v)2.3a and Ca(v)2.3e, in DRG neurons. Single-cell RT-PCR detected the expression of Ca(v)2.3e mRNA in 20% (n=14/70) of DRG neurons, relative to Ca(v)2.3a expression in 2.8% (n=2/70) of DRG neurons. Ca(v)2.3e mRNA was mainly detected in small-sized neurons (n=12/14), but in only a few medium-sized neurons (n=2/14) and not in large-sized neurons, indicating the prominence of Ca(v)2.3e in nociceptive DRG neurons. Moreover, Ca(v)2.3e was preferentially expressed in tyrosine-kinase A (trkA)-positive, iso-lectin B4 (IB4)-negative and transient receptor potential vanilloid 1 (TRPV1)-positive neurons. These results suggest that Ca(v)2.3e may be the main R-type Ca2+ channel isoform in nociceptive DRG neurons and thereby a potential target for pain treatment, not only in the trigerninal system but also in the spinal system.