Intracellular calcium signaling regulates glomerular filtration barrier permeability: the role of the PKGIα-dependent pathway

Podocytes are dynamic polarized cells that lie on the surface of glomerular capillaries and comprise an essential component of the glomerular filtration barrier. Insulin provoked a sustained, approximately 70%, increase in intracellular calcium concentration in podocytes. RT-PCR revealed the presence of mRNA encoding sarco/endoplasmic reticulum calcium ATPase isoforms 1-3, and plasma membrane Ca2+ pump (PMCA) isoforms 1,3,4; mRNA levels were depressed by the addition of insulin. Inhibitors of PMCA, and the Na+-Ca2+ exchanger, increased podocyte permeability to albumin, induced dimerization of protein kinase G type I alpha (PKGI alpha), and activation of PKGI alpha-dependent signaling. These data suggest the involvement of calcium and PKGI alpha signaling in insulin-enhanced filtration barrier permeability in podocytes.