Kramer Audra A, Ingraham Nicholas E, Sharpe Emily J, Mynlieff Michelle
Department of Biological Sciences, Marquette University, P.O. Box 1881, Milwaukee, WI 53201, USA ; Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
J Signal Transduct. 2012;2012:597214. doi: 10.1155/2012/597214. Epub 2012 Oct 14.
Influx of calcium through voltage-dependent channels regulates processes throughout the nervous system. Specifically, influx through L-type channels plays a variety of roles in early neuronal development and is commonly modulated by G-protein-coupled receptors such as GABA(B) receptors. Of the four isoforms of L-type channels, only Ca(V)1.2 and Ca(V)1.3 are predominately expressed in the nervous system. Both isoforms are inhibited by the same pharmacological agents, so it has been difficult to determine the role of specific isoforms in physiological processes. In the present study, Western blot analysis and confocal microscopy were utilized to study developmental expression levels and patterns of Ca(V)1.2 and Ca(V)1.3 in the CA1 region of rat hippocampus. Steady-state expression of Ca(V)1.2 predominated during the early neonatal period decreasing by day 12. Steady-state expression of Ca(V)1.3 was low at birth and gradually rose to adult levels by postnatal day 15. In immunohistochemical studies, antibodies against Ca(V)1.2 and Ca(V)1.3 demonstrated the highest intensity of labeling in the proximal dendrites at all ages studied (P1-72). Immunohistochemical studies on one-week-old hippocampi demonstrated significantly more colocalization of GABA(B) receptors with Ca(V)1.2 than with Ca(V)1.3, suggesting that modulation of L-type calcium current in early development is mediated through Ca(V)1.2 channels.
通过电压依赖性通道的钙内流调节着整个神经系统的过程。具体而言，通过L型通道的内流在神经元早期发育中发挥多种作用，并且通常受到G蛋白偶联受体（如GABA(B)受体）的调节。在L型通道的四种亚型中，只有Ca(V)1.2和Ca(V)1.3在神经系统中大量表达。这两种亚型都受到相同药理剂的抑制，因此很难确定特定亚型在生理过程中的作用。在本研究中，利用蛋白质免疫印迹分析和共聚焦显微镜来研究大鼠海马体CA1区中Ca(V)1.2和Ca(V)1.3的发育表达水平和模式。Ca(V)1.2的稳态表达在新生儿早期占主导地位，到第12天时下降。Ca(V)1.3的稳态表达在出生时较低，并在出生后第15天逐渐上升至成年水平。在免疫组织化学研究中，针对Ca(V)1.2和Ca(V)1.3的抗体在所研究的所有年龄段（P1 - 72）的近端树突中显示出最高的标记强度。对一周大的海马体进行的免疫组织化学研究表明，GABA(B)受体与Ca(V)1.2的共定位明显多于与Ca(V)1.3的共定位，这表明早期发育中L型钙电流的调节是通过Ca(V)1.2通道介导的。
