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

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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; Torrente, Angelo; Vandael, David; Pirone, Antonella.

I: Trends in Pharmacological Sciences, Vol. 32, Nr. 6, 2011, s. 366-375.

Forskningsoutput: TidskriftsbidragÖversiktsartikel

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Zuccotti, Annalisa ; Clementi, Stefano ; Reinbothe, Thomas ; Torrente, Angelo ; Vandael, David ; Pirone, Antonella. / Structural and functional differences between L-type calcium channels: crucial issues for future selective targeting. I: Trends in Pharmacological Sciences. 2011 ; Vol. 32, Nr. 6. s. 366-375.

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TY - JOUR

T1 - Structural and functional differences between L-type calcium channels: crucial issues for future selective targeting

AU - Zuccotti, Annalisa

AU - Clementi, Stefano

AU - Reinbothe, Thomas

AU - Torrente, Angelo

AU - Vandael, David

AU - Pirone, Antonella

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - voltage-gated calcium channels

KW - L-type

KW - isoforms

KW - Cav1.2

KW - Cav1.3

KW - drug development

KW - drug targets

U2 - 10.1016/j.tips.2011.02.012

DO - 10.1016/j.tips.2011.02.012

M3 - Review article

C2 - 21450352

VL - 32

SP - 366

EP - 375

JO - Trends in Pharmacological Sciences

JF - Trends in Pharmacological Sciences

SN - 0165-6147

IS - 6

ER -