Structural and functional differences between L-type calcium channels: crucial issues for future selective targeting

Summary, in English

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.

• Författare: Annalisa Zuccotti; Stefano Clementi; Thomas Reinbothe; Angelo Torrente; David Vandael; Antonella Pirone
• Avdelning/ar: Diabetes - öpatofysiologi; EXODIAB: Excellence of Diabetes Research in Sweden
• Publiceringsår: 2011
• Språk: Engelska
• Sidor: 366-375
• Publikation/Tidskrift/Serie: Trends in Pharmacological Sciences
• Volym: 32
• Issue: 6
• Länkar: http://dx.doi.org/10.1016/j.tips.2011.02.012
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Endocrinology and Diabetes
• Nyckelord: voltage-gated calcium channels; L-type; isoforms; Cav1.2; Cav1.3; drug development; drug targets
• Status: Published
• Forskningsgrupp: Diabetes - Islet Patophysiology
• ISBN/ISSN/Övrigt: ISSN: 0165-6147