title: Structural and functional differences between L-type calcium channels: crucial issues for future selective targeting.
abstract: Within the family of voltage-gated calcium channels (VGCCs), L-type channels (L-VGCCs) represent a well-established therapeutic target for calcium channel blockers, which are widely used to treat hypertension and myocardial ischemia. L-VGCCs outside the cardiovascular system also control key physiological processes such as neuronal plasticity, sensory cell function (e.g. in the inner ear and retina) and endocrine function (e.g. in pancreatic beta cells and adrenal chromaffin cells). Research into L-VGCCs was stimulated by the discovery that the known L-VGCC isoforms (Ca(V)1.1, Ca(V)1.2, Ca(V)1.3 and Ca(V)1.4) possess different biophysical properties. However, no L-VGCC-isoform-selective drugs have yet been identified. In this review, we examine Ca(V)1.2 and Ca(V)1.3 isoforms at the level of genetic structure, splice variants, post-translational modifications and functional protein coupling. We discuss candidate Ca(V)1.2- and Ca(V)1.3-specific characteristics as future therapeutic targets in individual organs.
authors: University of Tübingen, Department of Otolaryngology, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, Elfriede-Aulhorn-Str. 5, 72076 Tübingen, Germany. annalisazuccotti@gmail.com
authors: Annalisa
authors: A
authors: Zuccotti
authors: Stefano
authors: S
authors: Clementi
authors: Thomas
authors: T
authors: Reinbothe
authors: Angelo
authors: A
authors: Torrente
authors: David H
authors: DH
authors: Vandael
authors: Antonella
authors: A
authors: Pirone
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits; D016415:Sequence Alignment; D017385:Sequence Homology; D015398:Signal Transduction
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D021122:Protein Subunits; D002118:Calcium