Liao Ping, Zhang Heng Yu, Soong Tuck Wah
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
Pflugers Arch. 2009 Jul;458(3):481-7. doi: 10.1007/s00424-009-0635-5. Epub 2009 Jan 17.
Recent developments in the diversification of voltage-gated calcium channel function center on the rapidly emerging role of the posttranscriptional mechanism of alternative splicing. A number of diseases have been found to relate to the dysfunction of alternatively spliced exons arising from either genetic mutations or alterations in the splicing machinery. Mutations in some genes associated with congenital diseases have been detected to reside in alternatively spliced exons. As such, the severity of tissue-selective pathology of the disease will depend on the level of expression of the alternatively spliced exons in that tissue, as well as the extent in the change in channel properties. Importantly, alteration in channel properties is affected by the backbone array of the combinatorial alternatively spliced exons within the channel. In other words, the context by which mutations or alternatively spliced exons are expressed is a great influence on the alteration of channel properties and as such physiology and disease. We reviewed here recent comprehension of alternative splicing of voltage-gated calcium channels and how such structural and functional diversity of voltage-gated calcium channels will aid to clarify the pathophysiology of relevant diseases. Such understandings will further provide guidance for novel treatment.
电压门控钙通道功能多样化的最新进展集中在快速兴起的可变剪接转录后机制的作用上。已发现许多疾病与由基因突变或剪接机制改变引起的可变剪接外显子功能障碍有关。已检测到一些与先天性疾病相关的基因中的突变存在于可变剪接外显子中。因此，该疾病组织选择性病理的严重程度将取决于该组织中可变剪接外显子的表达水平，以及通道特性变化的程度。重要的是，通道特性的改变受通道内组合可变剪接外显子的主干阵列影响。换句话说，突变或可变剪接外显子的表达背景对通道特性的改变以及生理和疾病有很大影响。我们在此回顾了对电压门控钙通道可变剪接的最新理解，以及电压门控钙通道的这种结构和功能多样性将如何有助于阐明相关疾病的病理生理学。这些理解将进一步为新的治疗提供指导。
