title: Cardiac functions of voltage-gated Ca(2+) channels: role of the pharmacoresistant type (E-/R-Type) in cardiac modulation and putative implication in sudden unexpected death in epilepsy (SUDEP).
abstract: Voltage-gated Ca(2+) channels (VGCCs) are ubiquitous in excitable cells. These channels play key roles in many physiological events like cardiac regulation/pacemaker activity due to intracellular Ca(2+) transients. In the myocardium, the Cav1 subfamily (L-type: Cav1.2 and Cav1.3) is the main contributor to excitation-contraction coupling and/or pacemaking, whereas the Cav3 subfamily (T-type: Cav3.1 and Cav3.2) is important in rhythmically firing of the cardiac nodal cells. No established cardiac function has been attributed to the Cav2 family (E-/R-type: Cav2.3) despite accumulating evidence of cardiac dysregulation observed upon deletion of the Cav2.3 gene, the only member of this family so far detected in cardiomyocytes. In this review, we summarize the pathophysiological changes observed after ablation of the E-/R-type VGCC and propose a cardiac mechanism of action for this channel. Also, considering the role played by this channel in epilepsy and its reported sensitivity to antiepileptic drugs, a putative involvement of this channel in the cardiac mechanism of sudden unexpected death in epilepsy is also discussed.
authors.affiliation: Institute of Neurophysiology, University of Köln, Robert-Koch-Str. 39, D-50931, Köln, Germany, tevoufoe@uni-koeln.de.
authors.forename: Etienne E
authors.initials: EE
authors.lastname: Tevoufouet
authors.forename: Erastus N
authors.initials: EN
authors.lastname: Nembo
authors.forename: Maxine
authors.initials: M
authors.lastname: Dibué-Adjei
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Filomain
authors.initials: F
authors.lastname: Nguemo
authors.forename: Toni
authors.initials: T
authors.lastname: Schneider
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000502:physiology*; D020908:Calcium Channels, R-Type / Q000737:chemistry / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000737:chemistry / Q000502:physiology*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000502:physiology*; D003645:Death, Sudden / Q000209:etiology*; D004827:Epilepsy / Q000150:complications / Q000503:physiopathology*; D006321:Heart / Q000502:physiology*; D006801:Humans
chemical_list: C423009:CACNA1E protein, human; D020746:Calcium Channels, L-Type; D020908:Calcium Channels, R-Type; D020747:Calcium Channels, T-Type; D027682:Cation Transport Proteins