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

Research output: Contribution to journalReview article

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.

Details

Authors
  • Annalisa Zuccotti
  • Stefano Clementi
  • Thomas Reinbothe
  • Angelo Torrente
  • David Vandael
  • Antonella Pirone
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes

Keywords

  • voltage-gated calcium channels, L-type, isoforms, Cav1.2, Cav1.3, drug development, drug targets
Original languageEnglish
Pages (from-to)366-375
JournalTrends in Pharmacological Sciences
Volume32
Issue number6
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes

Related research output

Thomas Reinbothe, 2011, Department of Clinical Sciences, Lund University. 154 p.

Research output: ThesisDoctoral Thesis (compilation)

View all (1)