National Research Laboratory for Pain, Dental Research Institute and Department of Physiology School of Dentistry, Seoul National University, Seoul 110-749, Korea.
Korean J Physiol Pharmacol. 2010 Feb;14(1):45-9. doi: 10.4196/kjpp.2010.14.1.45. Epub 2010 Feb 28.
R-type Ca(v)2.3 high voltage-activated Ca(2+) 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~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, isolectin 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 Ca(2+) channel isoform in nociceptive DRG neurons and thereby a potential target for pain treatment, not only in the trigeminal system but also in the spinal system.
R 型钙通道(Ca(v)2.3)在周围感觉神经元中可被高电压激活,有助于疼痛的传递。最近我们已经证明,在六种 Ca(v)2.3 亚型(Ca(v)2.3a~Ca(v)2.3e)中,Ca(v)2.3e 亚型主要在三叉神经节(TG)伤害性神经元中表达。在本研究中,我们进一步研究了 Ca(v)2.3 亚型在背根神经节(DRG)神经元中的表达模式。与在 TG 神经元中一样,全组织 RT-PCR 分析显示 DRG 神经元中存在两种亚型 Ca(v)2.3a 和 Ca(v)2.3e。单细胞 RT-PCR 检测到 Ca(v)2.3e mRNA 在 20%(n=14/70)的 DRG 神经元中表达,而 Ca(v)2.3a 在 2.8%(n=2/70)的 DRG 神经元中表达。Ca(v)2.3e mRNA 主要在小神经元(n=12/14)中检测到,但在少数中神经元(n=2/14)和大神经元(n=2/70)中未检测到,表明 Ca(v)2.3e 在伤害性 DRG 神经元中占优势。此外,Ca(v)2.3e 优先在酪氨酸激酶 A(trkA)阳性、异凝集素 B4(IB4)阴性和瞬时受体电位香草酸 1(TRPV1)阳性神经元中表达。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,也是治疗疼痛的潜在靶点,不仅在三叉神经系统,而且在脊髓系统。