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

Zuccotti, Annalisa; Clementi, Stefano; Reinbothe, Thomas LU ; Torrente, Angelo; Vandael, David and Pirone, Antonella (2011) In Trends in Pharmacological Sciences 32(6). p.366-375
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
voltage-gated calcium channels, L-type, isoforms, Cav1.2, Cav1.3, drug development, drug targets
in
Trends in Pharmacological Sciences
volume
32
issue
6
pages
366 - 375
publisher
Elsevier
external identifiers
  • wos:000291843800007
  • scopus:79957685488
ISSN
0165-6147
DOI
10.1016/j.tips.2011.02.012
language
English
LU publication?
yes
id
99d58ca6-42f9-4a03-aef1-3ecd311d5323 (old id 1963267)
date added to LUP
2012-01-19 11:46:00
date last changed
2017-11-12 03:03:25
@article{99d58ca6-42f9-4a03-aef1-3ecd311d5323,
  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.},
  author       = {Zuccotti, Annalisa and Clementi, Stefano and Reinbothe, Thomas and Torrente, Angelo and Vandael, David and Pirone, Antonella},
  issn         = {0165-6147},
  keyword      = {voltage-gated calcium channels,L-type,isoforms,Cav1.2,Cav1.3,drug development,drug targets},
  language     = {eng},
  number       = {6},
  pages        = {366--375},
  publisher    = {Elsevier},
  series       = {Trends in Pharmacological Sciences},
  title        = {Structural and functional differences between L-type calcium channels: crucial issues for future selective targeting},
  url          = {http://dx.doi.org/10.1016/j.tips.2011.02.012},
  volume       = {32},
  year         = {2011},
}