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

我们已经表征了P/ q型Ca2^<2+>通道的功能缺陷，这些缺陷是由形成孔隙的α _<14> (BI)亚基中的失稳突变totering （tg）和leaner （tg-la）引起的。在这两种突变中，引起更严重的失调的tg-la对P/Q-typeCa2^<2+>通道的生物物理特性的影响更严重。该基因的突变也可引起癫痫和共济失调，它编码了一种新的神经元γ异构体gamma_2。G蛋白亚基与细胞内Ca2^<2+>释放通道（ryanodine受体）的相互作用位点被定位在Ca2^<2+>通道α 1亚基的细胞质区域。此外，我们从小鼠大脑中分离出一个新的受体激活通道TRP5。TRP5被受体刺激激活，其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.