@article{oai:soar-ir.repo.nii.ac.jp:00020248, author = {Ohno, Shoko and Yokoi, Hideki and Mori, Kiyoshi and Kasahara, Masato and Kuwahara, Koichiro and Fujikura, Junji and Naito, Masaki and Kuwabara, Takashige and Imamaki, Hirotaka and Ishii, Akira and Saleem, Moin A. and Numata, Tomohiro and Mori, Yasuo and Nakao, Kazuwa and Yanagita, Motoko and Mukoyama, Masashi}, journal = {SCIENTIFIC REPORTS}, month = {Jun}, note = {Pharmacological blockade of the N- and L-type calcium channel lessens renal injury in kidney disease patients. The significance of specific blockade of α1 subunit of N-type calcium channel, Cav2.2, in diabetic nephropathy, however, remains to be clarified. To examine functional roles, we mated Cav2.2?/? mice with db/db (diabetic) mice on the C57BLKS background. Cav2.2 was localized in glomeruli including podocytes and in distal tubular cells. Diabetic Cav2.2?/? mice significantly reduced urinary albumin excretion, glomerular hyperfiltration, blood glucose levels, histological deterioration and systolic blood pressure (SBP) with decreased urinary catecholamine compared to diabetic Cav2.2+/+ mice. Interestingly, diabetic heterozygous Cav2.2+/? mice also decreased albuminuria, although they exhibited comparable systolic blood pressure, sympathetic nerve activity and creatinine clearance to diabetic Cav2.2+/+ mice. Consistently, diabetic mice with cilnidipine, an N-/L-type calcium channel blocker, showed a reduction in albuminuria and improvement of glomerular changes compared to diabetic mice with nitrendipine. In cultured podocytes, depolarization-dependent calcium responses were decreased by ω-conotoxin, a Cav2.2-specific inhibitor. Furthermore, reduction of nephrin by transforming growth factor-β (TGF-β) in podocytes was abolished with ω-conotoxin, cilnidipine or mitogen-activated protein kinase kinase inhibitor. In conclusion, Cav2.2 inhibition exerts renoprotective effects against the progression of diabetic nephropathy, partly by protecting podocytes., Article, SCIENTIFIC REPORTS. 6: 27192(2016)}, title = {Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure}, volume = {6}, year = {2016} }