Non-voltage-gated Ca Channel Signaling in Glomerular Cells in Kidney Health and Disease

Positioned at the head of the nephron, the renal corpuscle generates a plasma ultrafiltrate to initiate urine formation. Three major cell types within the renal corpuscle, the glomerular mesangial cells, podocytes, and glomerular capillary endothelial cells, communicate via endocrine- and paracrine-signaling mechanisms to maintain the structure and function of the glomerular capillary network and filtration barrier. Ca signaling mediated by several distinct plasma membrane Ca channels impacts the functions of all three cell types. The past two decades have witnessed pivotal advances in understanding of non-voltage-gated Ca channel function and regulation in the renal corpuscle in health and renal disease. This review summarizes the current knowledge of the physiological and pathological impact of non-voltage-gated Ca channel signaling in mesangial cells, podocytes and glomerular capillary endothelium. The main focus is on transient receptor potential and store-operated Ca channels, but ionotropic -methyl-d-aspartate receptors and purinergic receptors also are discussed. This update of Ca channel functions and their cellular signaling cascades in the renal corpuscle is intended to inform the development of therapeutic strategies targeting these channels to treat kidney diseases, particularly diabetic nephropathy.