High-voltage-activated calcium current and its modulation by dopamine D_4 and pituitary adenylate cyclase activating polypeptide receptors in cerebellar granule cells

小脑颗粒细胞是离体单细胞水平中枢神经元生物学研究的理想模型．随着细胞发育，其ＨＶＡ钙电流的基因表达、门控性质和药理学特征发生明显变化，提示钙电流涉及颗粒细胞的成熟和兴奋性的产生．多巴胺通过激活膜上的Ｄ４受体抑制Ｌ型钙电流，这种抑制效应并不需要腺苷酸环化酶系统的参与．功能性Ｄ４受体的首次发现不仅有助于研究抗精神病药，更揭示了多巴胺也参与小脑神经元之间的兴奋传递过程．ＰＡＣＡＰ则通过激活其Ｉ受体增加钙内流和钙库的释放使胞浆内钙浓度提高，ＰＡＣＡＰ的钙通道刺激效应可能需要ＰＬＣ系统的介导，并与颗粒细胞的成熟和成活有关．

Cerebellar granule cells were a good mold for electrophysiologic studies at the single neuron level. Two distinct types of high voltage activated Ca 2+ channels were present in ce￣rebellar granule cells. These calcium chan￣nels change their expression, gating, and pharma￣co￣logical properties during development, suggestiog that calcium channel must be related to the processes of granule cell maturation and excitability. Dopamine inhibited L type calcium current by activating D 4 receptor, and this effect might involve another signaling system with the exception of cAMP system. The functional D 4 receptor discovered in cerebellum not only gave a possibility to find other antipsychotics, but also supported the existence of a dopaminergic system in the granule cell involving the D 4 receptor. Pituitary adenylate cyclase activating polypeptide (PACAP) could increase intra￣cel￣lular Ca 2+ content by activation of Ca 2+ channel and mobilization of intracellular Ca 2+ stores. The effects were also cAMP independent. Activating Ca 2+ currents might be an important and necessary role of PACAP as a neurotropic factor involved in the control of multiplication, differentiation, and migration of granule cells.