High-voltage-activated calcium current and its modulation by dopamine D4 and pituitary adenylate cyclase activating polypeptide receptors in cerebellar granule cells

Cerebellar granule cells were a good mold for electrophysiologic studies at the single neuron level. Two distinct types of high-voltage-activated Ca2+ channels were present in cerebellar granule cells. These calcium channels change their expression, gating, and pharmacological properties during development, suggesting that calcium channel must be related to the processes of granule cell maturation and excitability. Dopamine inhibited L-typecalcium current by activating D4 receptor, and this effect might involve another signaling system with the exception of cAMP system. The functional D4 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 D4 receptor. Pituitary adenylate cyclase activating polypeptide (PACAP) could increase intracellular Ca2+ content by activation of Ca2+ channel and mobilization of intracellular Ca2+ stores. The effects were also cAMP-independent. Activating Ca2+ 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.