Role of calcium in gentamicin-induced mesangial cell activation

Gentamicin-induced decreases in glomerular filtration rate have been associ ated to a marked decline in the glomerular capillary ultrafiltration coeffi cient which could be due to an active contraction of mesangial cells. In th e present work we assessed a possible role of cytosolic Ca2+ as a mediator that leads to contraction and proliferation induced by gentamicin on mesang ial cells. Gentamicin (10(-5)M) induced an increase in cytosolic free Ca2+, that was fully inhibited by the calcium channel blocker, verapamil, and by the endoplasmic reticulum calcium release blocker, TMB-8. Gentamicin induc ed a planar surface area reduction in cultured mesangial cells, that was bl unted by verapamil and TMB-8. Gentamicin also stimulated [H-3]thymidine inc orporation into DNA and increased viable cell number, effects that were red uced by both, verapamil and TMB-8. Gentamicin stimulated the expression of the AP1 protein; this expression was partially blunted by verapamil and TMB -8. Moreover, verapamil inhibited gentamicin-induced PAF synthesis from mes angial cells. in summary, gentamicin directly raised intracellular Ca2+ act ivating both calcium influx from external medium and calcium release from i nternal stores. This increase is responsible of cellular activation (contra ction and proliferation) and PAF synthesis induced by gentamicin on mesangi al cells. Copyright (C) 2000 S. Karger AG, Basel.