Levels of Ca(V)1.2 L-Type Ca(2+) Channels Peak in the First Two Weeks in Rat Hippocampus Whereas Ca(V)1.3 Channels Steadily Increase through Development.
Levels of Ca(V)1.2 L-Type Ca(2+) Channels Peak in the First Two Weeks in Rat Hippocampus Whereas Ca(V)1.3 Channels Steadily Increase through Development.
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DOI：
10.1155/2012/597214
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Mynlieff M
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文献类型：
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作者：
Kramer AA;Ingraham NE;Sharpe EJ;Mynlieff M
钙离子通过电压依赖通道的内流调节整个神经系统的过程。具体地说，通过L类通道的内流在早期神经元发育中发挥着多种作用，通常受到G蛋白偶联受体(如GAAB受体)的调节。在L类通道的四种亚型中，只有CaV1.2和CaV1.3在神经系统中主要表达。这两种异构体都被相同的药物抑制，因此很难确定特定的异构体在生理过程中的作用。本研究利用Western印迹分析和共聚焦显微镜技术研究了CaV1.2和CaV1.3在大鼠海马CA1区的发育性表达水平和模式。在出生后12天，CaV1.2的稳定表达占主导地位。出生时，CaV1.3的稳定表达很低，到出生后15天，CaV1.3的稳定表达逐渐上升到成人水平。在免疫组织化学研究中，抗CaV1.2和CaV1.3的抗体在所有年龄组的近侧树突中的标记强度最高(P1-72)。免疫组织化学研究显示，GAAB受体与CaV1.2共定位明显多于CaV1.3，提示发育早期L型钙电流的调节是通过CaV1.2通道介导的。
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 GABAB receptors. Of the four isoforms of L-type channels, only CaV1.2 and CaV1.3 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 CaV1.2 and CaV1.3 in the CA1 region of rat hippocampus. Steady-state expression of CaV1.2 predominated during the early neonatal period decreasing by day 12. Steady-state expression of CaV1.3 was low at birth and gradually rose to adult levels by postnatal day 15. In immunohistochemical studies, antibodies against CaV1.2 and CaV1.3 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 GABAB receptors with CaV1.2 than with CaV1.3, suggesting that modulation of L-type calcium current in early development is mediated through CaV1.2 channels.