Advances in L-Type Calcium Channel Structures, Functions and Molecular Modeling

Abstract

L-type Calcium Channels (LTCCs), also termed as Ca_v1, belong to voltage-gated calcium channels (VGCCs/Ca_vs), which play a critical role in a wide spectrum of physiological processes, including neurotransmission, cell cycle, muscular contraction, cardiac action potential and gene expression. Aberrant regulation of calcium channels is involved in neurological, cardiovascular, muscular and psychiatric disorders. Accordingly, LTCCs have been regarded as important drug targets, and a number of LTCC drugs are in clinical use. In this review, the recent development of structures and biological functions of LTCCs are introduced. Moreover, the representative modulators and ligand binding sites of LTCCs are discussed. Finally, molecular modeling and Computer-aided Drug Design (CADD) methods for understanding structure-function relations of LTCCs are summarized.

Keywords: L-type calcium channels; computer-aided drug design; drugbinding sites; isoform-selective VGCC modulators; molecular modeling; voltage-gated calcium channels.