The effect of Cyclin‐dependent kinase 5 on voltage‐dependent calcium channels in PC 12 cells varies according to channel type and cell differentiation state

Cyclin‐dependent kinase 5 (Cdk5) is a Ser/Thr kinase that plays an important role in the release of neurotransmitter from pre‐synaptic terminals triggered by Ca 2+ influx into the pre‐synaptic cytoplasm through voltage‐dependent Ca 2+ channels ( VDCC s). It is reported that Cdk5 regulates L‐, P/Q‐, or N‐type VDCC , but there is conflicting data as to the effect of Cdk5 on VDCC activity. To clarify the mechanisms involved, we examined the role of Cdk5 in regulating the Ca 2+ ‐channel property of VDCC s, using PC 12 cells expressing endogenous, functional L‐, P/Q‐, and N‐type VDCC s. The Ca 2+ influx, induced by membrane depolarization with high K + , was monitored with a fluorescent Ca 2+ indicator protein in both undifferentiated and nerve growth factor ( NGF )‐differentiated PC 12 cells. Overall, Ca 2+ influx was increased by expression of Cdk5‐p35 in undifferentiated PC 12 cells but suppressed in differentiated PC 12 cells. Moreover, we found that different VDCC s are distinctly regulated by Cdk5‐p35 depending on the differentiation states of PC 12 cells. These results indicate that Cdk5‐p35 regulates L‐, P/Q‐, or N‐type VDCC s in a cellular context‐dependent manner.Calcium (Ca 2+ ) influx through voltage‐dependent Ca 2+ channels (VDCCs) triggers neurotransmitter release from pre‐synaptic terminal of neurons. The channel activity of VDCCs is regulated by Cdk5‐p35, a neuronal Ser/Thr kinase. However, there have been debates about the regulation of VDCCs by Cdk5. Using PC12 cells, we show that Cdk5‐p35 regulates VDCCs in a type (L, P/Q, and N) and differentiation‐dependent manner. NGF = nerve growth factor.