Voltage-Dependent Calcium Channels, Calcium Binding Proteins, and Their Interaction in the Pathological Process of...

As an important second messenger, the calcium ion (Ca2+) plays a vital role in normal brain function and in the pathophysiological process of different neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and epilepsy. Ca2+ takes part in the regulation of neuronal excitability, and the imbalance of intracellular Ca2+ is a trigger factor for the occurrence of epilepsy. Several anti-epileptic drugs target voltage-dependent calcium channels (VDCCs). Intracellular Ca2+ levels are mainly controlled by VDCCs located in the plasma membrane, the calcium-binding proteins (CBPs) inside the cytoplasm, calcium channels located on the intracellular calcium store (particular the endoplasmic reticulum/sarcoplasmic reticulum), and the Ca2+-pumps located in the plasma membrane and intracellular calcium store. So far, while many studies have established the relationship between calcium control factors and epilepsy, the mechanism of various Ca2+ regulatory factors in epileptogenesis is still unknown. In this paper, we reviewed the function, distribution, and alteration of VDCCs and CBPs in the central nervous system in the pathological process of epilepsy. The interaction of VDCCs with CBPs in the pathological process of epilepsy was also summarized. We hope this review can provide some clues for better understanding the mechanism of epileptogenesis, and for the development of new anti-epileptic drugs targeting on VDCCs and CBPs.