Regulation of T-type calcium channels: signalling pathways and functional implications.
T-type calcium channels (T-channels) contribute to a wide variety of physiological functions, especially in the cardiovascular and nervous systems. Recent studies using knock-out mouse models have been instrumental in documenting further the role of T-channels in sleep, heartbeat, pain and epilepsy. Importantly, several novel aspects of the regulation of these channels have been identified over the last few years, providing new insights into their physiological and pathophysiological roles. Here, we review recent evidence supporting that the Cav3 subunits of T-channels are modulated by endogenous ligands such as anandamide, zinc, redox and oxidizing agents, as well as G-protein and protein kinases pathways. The study of T-channel mutations associated with childhood absence epilepsy has also revealed new aspects of Cav3 subunit trafficking. Collectively, these findings identify novel regulatory mechanisms involved in the fine tuning of T-channel expression and activity, and offer new directions for the design of novel therapeutic strategies targeting these channels.
Huc
Sylvaine
S
Centre National de la Recherche Scientifique, UMR 5203, Institut de Génomique Fonctionnelle, Département de Physiologie, Montpellier, 34094 Montpellier, France.
Monteil
Arnaud
A
Bidaud
Isabelle
I
Barbara
Guillaume
G
Chemin
Jean
J
Lory
Philippe
P
D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053447:Channelopathies / Q000235:genetics / Q000378:metabolism; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D015398:Signal Transduction / Q000502:physiology*
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D020033:Protein Isoforms