CA2-PERMEABLE CHANNEL ASSOCIATED WITH PLATELET-DERIVED GROWTH-FACTOR RECEPTOR IN MESANGIAL CELLS()

We used patch-clamp methods to study the effect of platelet-derived gr owth factor (PDGF) on Ca2+ entry in cultured rat glomerular mesangial cells. In cell-attached patches, application of 50 ng/ml PDGF-BB insid e, but not outside, the pipette frequently induced channel openings. T he unitary conductance was 0.67 +/- 0.09 pS (n = 8) with 110 mM Mn2+ a nd 1.03 +/- 0.19 pS (n = 11) with 110 mM Ca2+ as the charge carrier. N umber of channels times open probability was 0.515 +/- 0.144 (n = 14) with intrapipette PDGF and 0.037 +/- 0.022 (n = 12) without. Channel k inetics were only slightly voltage dependent. There was no effect of r eplacing chloride with gluconate in excised inside-out patches, showin g that the channel was cation selective. The permeability (P) ratio fo r P-Mn/P-Na was 1.65 and for P-Ca/P-Na was 1.24. With the use of ampho tericin B ''perforated'' whole cell patches, PDGF induced a small inwa rd current (-16.1 +/- 4.33 pA; n = 11, membrane potential = -70 mV) co nsistent with 3,000-4,000 channels/cell. In summary, we have described a very-low-conductance Ca2+-permeable channel in rat mesangial cells with the following properties. 1) Activation by PDGF-BB occurs only wh en applied in close proximity to the channel. 2) Once activated, open probability is only slightly voltage dependent. 3) Under normal circum stances, the channel would probably appear to be cation nonselective, but with a permeability tb divalent more than monovalent cations. 4) T his PDGF-induced channel could provide a ligand-gated pathway for Ca2 entry into mesangial cells that does not require membrane depolarizat ion.