Glomerular Mesangial Cells: Electrophysiology and Regulation of Contraction

Stockand, James D., and Steven C. Sansom. Glomerular Mesangial Cells: Electrophysiology and Regulation of Contraction. Physiol. Rev. 78: 723–744, 1998. — Mesangial cells are smooth muscle-like pericytes that abut and surround the filtration capillaries within the glomerulus. Studies of the fine ultrastructure of the glomerulus show that the mesangial cell and the capillary basement membrane form a biomechanical unit capable of regulating filtration surface area as well as intraglomerular blood volume. Structural and functional studies suggest that mesangial cells regulate filtration rate in both a static and dynamic fashion. Mesangial excitability enables a homeostatic intraglomerular stretch reflex that integrates an increase in filtration pressure with a reduction in capillary surface area. In addition, mesangial tone is regulated by diverse vasoactive hormones. Agonists, such as angiotensin II, contract mesangial cells through a signal transduction pathway that releases intracellular stores of Ca 2+ , which subsequently activate nonselective cation channels and Cl − channels to depolarize the plasma membrane. The change in membrane potential activates voltage-gated Ca 2+ channels, allowing Ca 2+ cell entry and further activation of depolarizing conductances. Contraction and entry of cell Ca 2+ are inhibited only when Ca 2+ -activated K + channels (BK Ca ) are activated and the membrane is hyperpolarized toward the K + equilibrium potential. The mesangial BK Ca is a weak regulator of contraction in unstimulated cells; however, the gain of the feedback is increased by atrial natriuretic peptide, nitric oxide, and the second messenger cGMP, which activates protein kinase G and decreases both the voltage and Ca 2+ activation thresholds of BK Ca independent of sensitivity. This enables BK Ca to more effectively counter membrane depolarization and voltage-gated Ca 2+ influx. After hyperpolarizing the membrane, BK Ca rapidly inactivates because of dephosphorylation by protein phosphatase 2A. Regulation of ion channels has been linked casually to hyperfiltration during early stages of diabetes mellitus. Determining the signaling pathways controlling the electrophysiology of glomerular mesangial cells is important for understanding how glomerular filtration rate is regulated in health and disease.