Ludwig A, Flockerzi V, Hofmann F
Institut für Pharmakologie und Toxikologie der Technischen Universität München, 80802 München, Germany.
J Neurosci. 1997 Feb 15;17(4):1339-49. doi: 10.1523/JNEUROSCI.17-04-01339.1997.
The neuronal high voltage-activated calcium channels are a family of ion channels composed from up to five different alpha1 and four different beta subunits. The neuronal distribution and subunit composition of calcium channels were investigated using subunit-specific antibodies and riboprobes. The beta subunit-specific antibodies identified the presence of beta1a in skeletal muscle; beta2 in heart; and beta2, beta3, and beta4 in brain. The beta3 protein was widely distributed in rat brain, with prominent labeling of olfactory bulb, cortex, hippocampus, and habenula. The beta4 protein was also widely expressed, most prominently in the cerebellum. beta2 protein was expressed at only low levels. In situ hybridization with beta subunit-specific riboprobes confirmed the differential expression pattern of the individual subunits. Hybridization with riboprobes specific for the alpha1A, alpha1B, alpha1C, and alpha1D subunits showed a broad distribution of alpha1A and alpha1B transcripts, whereas the expression level of alpha1C and alpha1D mRNA was lower and more spatially restricted. The overall expression pattern and cellular localization suggested that beta4 may associate predominantly, but probably not exclusively, with the alpha1A subunit, and beta3 with the alpha1B subunit. In certain brain areas such as the habenula, the beta3 subunit may associate with other alpha1 subunits too. Furthermore, the beta2 subunit may form complexes with different alpha1 subunits in brain and cardiac muscle. These results demonstrate that a given beta subunit may associate with different alpha1 subunits in a cell type-dependent manner, contributing to the diversity of the neuronal calcium channels.
神经元高电压激活钙通道是一类离子通道家族，由多达五种不同的α1亚基和四种不同的β亚基组成。利用亚基特异性抗体和核糖探针研究了钙通道的神经元分布和亚基组成。β亚基特异性抗体鉴定出骨骼肌中存在β1a；心脏中存在β2；大脑中存在β2、β3和β4。β3蛋白广泛分布于大鼠脑内，嗅球、皮层、海马和缰核有明显标记。β4蛋白也广泛表达，最显著的是在小脑中。β2蛋白仅低水平表达。用β亚基特异性核糖探针进行原位杂交证实了各个亚基的差异表达模式。与α1A、α1B、α1C和α1D亚基特异性核糖探针杂交显示α1A和α1B转录本广泛分布，而α1C和α1D mRNA的表达水平较低且空间分布更受限。整体表达模式和细胞定位表明，β4可能主要但可能并非唯一地与α1A亚基结合，β3与α1B亚基结合。在某些脑区如缰核中，β3亚基也可能与其他α1亚基结合。此外，β2亚基可能在脑和心肌中与不同的α1亚基形成复合物。这些结果表明，给定的β亚基可能以细胞类型依赖的方式与不同的α1亚基结合，从而导致神经元钙通道的多样性。
