Osanai Makoto, Saegusa Hironao, Kazuno An-a, Nagayama Shin, Hu Qiuping, Zong Shuqin, Murakoshi Takayuki, Tanabe Tsutomu
Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Biochem Biophys Res Commun. 2006 Jun 9;344(3):920-5. doi: 10.1016/j.bbrc.2006.03.206. Epub 2006 Apr 19.
Voltage-dependent Ca(2+) channels play important roles in cerebellar functions including motor coordination and learning. Since abundant expression of Ca(V)2.3 Ca(2+) channel gene in the cerebellum was detected, we searched for possible deficits in the cerebellar functions in the Ca(V)2.3 mutant mice. Behavioral analysis detected in delayed motor learning in rotarod tests in mice heterozygous and homozygous for the Ca(V)2.3 gene disruption (Ca(V)2.3+/- and Ca(V)2.3-/-, respectively). Electrophysiological analysis of mutant mice revealed perplexing results: deficit in long-term depression (LTD) at the parallel fiber Purkinje cell synapse in Ca(V)2.3+/- mice but apparently normal LTD in Ca(V)2.3-/- mice. On the other hand, the number of spikes evoked by current injection in Purkinje cells under the current-clamp mode decreased in Ca(V)2.3 mutant mice in a gene dosage-dependent manner, suggesting that Ca(V)2.3 channel contributed to spike generation in Purkinje cells. Thus, Ca(V)2.3 channel seems to play some roles in cerebellar functions.
电压依赖性钙通道在包括运动协调和学习在内的小脑功能中发挥着重要作用。由于在小脑中检测到Ca(V)2.3钙通道基因的大量表达，我们在Ca(V)2.3突变小鼠中寻找小脑功能可能存在的缺陷。行为分析在Ca(V)2.3基因破坏的杂合子和纯合子小鼠（分别为Ca(V)2.3+/-和Ca(V)2.3-/-）的转棒试验中检测到延迟运动学习。对突变小鼠的电生理分析得出了令人困惑的结果：Ca(V)2.3+/-小鼠中平行纤维浦肯野细胞突触处的长时程抑制（LTD）存在缺陷，但Ca(V)2.3-/-小鼠中的LTD明显正常。另一方面，在电流钳模式下，Ca(V)2.3突变小鼠中浦肯野细胞电流注入诱发的动作电位数量以基因剂量依赖的方式减少，这表明Ca(V)2.3通道有助于浦肯野细胞动作电位的产生。因此，Ca(V)2.3通道似乎在小脑功能中发挥着某些作用。
