Referenced in: none

Automatically associated channels: Cav3.2

Title: Inhibition of human mesangial cell proliferation by targeting T-type calcium channels.

Authors: Christopher J Mulgrew, Andrea Cove-Smith, Linda M McLatchie, Gavin Brooks, Michael J Shattock, Bruce M Hendry

Journal, date & volume: Nephron Exp. Nephrol., 2009 , 113, e77-88

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19672121

Abstract
Aberrant glomerular mesangial cell (MC) proliferation is a common finding in renal diseases. T-type calcium channels (T-CaCN) play an important role in the proliferation of a number of cell types, including vascular smooth muscle cells. The hypothesis that T-CaCN may play a role in the proliferation of human MC was investigated.The presence of T-CaCN in primary cultures of human MC was examined using voltage clamping and by RT-PCR. The effect of calcium channel inhibitors, and of siRNA directed against the Cav3.2 T-CaCN isoform, on MC proliferation was assessed using the microculture tetrazolium assay and nuclear BrdU incorporation.Human MC express only the Cav3.2 T-CaCN isoform. Co-incubation of MC with a T-CaCN inhibitor (mibefradil, TH1177 or Ni(2+)) results in a concentration-dependent attenuation of proliferation. This effect cannot be attributed to direct drug-induced cytotoxicity or apoptosis and is not seen with verapamil, an L-type channel blocker. Transfection of MC with siRNA results in knockdown of T-CaCN Cav3.2 mRNA and a clear attenuation of MC proliferation.These results demonstrate for the first time an important role for T-CaCN in human MC proliferation. This could potentially lead to a novel therapy in the treatment of proliferative renal diseases.