Production & analysis of Ca^<2+> channel subunit-defecient mice.

我们研究了由成孔α_lt；14&gt；(BI)亚基的共济失调突变(Tg)和瘦身(Tg-1a)引起的P/Q型钙通道的功能缺陷。在这两个突变中，引起更严重共济失调的Tg-1a对P/Q型钙通道的生物物理性质的影响比另一种更严重。该基因突变还可引起癫痫和共济失调，编码一种新的神经元伽马异构体Gamma_2。G蛋白亚基与胞内钙释放通道(Ryanodine受体)的相互作用部位被定位在钙通道α1亚基的细胞质区域。此外，我们从小鼠脑中分离到一种新的受体激活通道TRP5。TRP5是通过受体刺激而激活的，其激活机制与储存耗尽无关。

We have characterized functional defects of the P/Q-type Ca2^<2+> channels induced by the ataxic mutations tottering (tg) and leaner (tg-la) in the pore-forming alpha_<14> (BI) subunit. Of these two mutations, tg-la which causes more sever ataxia affected biophysical properties of the P/Q-typeCa2^<2+> channel more seriously than the other. The stargazer gene whose mutation cause also epilepsy and ataxia was shown to encode a novel neuronal gamma isoform gamma_2. The interaction sites of the G protein subunits and intracellular Ca2^<2+> release channel (ryanodine receptor)were mapped in the cytoplasmic regions of the Ca2^<2+> channel alpha1 subunits.In addition, we isolated a novel receptor-activated channel TRP5 from mouse brain. TRP5 was activated by receptor stimulation via a mechanism unrelated to store depletion.