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T-type Calcium Channels in Health and Disease

Author(s):

Dan Wang, Lotten Ragnarsson and Richard J. Lewis*   Pages 1 - 21 ( 21 )

Abstract:


Low voltage-activated (LVA) T-type calcium channels are characterized by transient current and low threshold spikes (LTS) that trigger neuronal firing and oscillatory behavior. Combined with their preferential localization in dendrites and their specific “window current”, T-type calcium channels are considered to be key players in signal amplification and synaptic integration. Assisted by the emerging pharmacological tools, the structural determinants of channel gating and kinetics, as well as novel physiological and pathological functions of T-type calcium channels, are being uncovered. In this review, we provide an overview of structural determinants in T-type calcium channels, their involvement in disorders and diseases, the development of novel channel modulators, as well as structure-activity relationship (SAR) studies that lead to rational drug design.

Keywords:

T-type calcium channels, structural determinants, channel function, pathophysiological roles, modulators, rational drug design

Affiliation:

Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, the University of Queensland, Brisbane Qld 4072, Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, the University of Queensland, Brisbane Qld 4072, Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, the University of Queensland, Brisbane Qld 4072



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