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 growth factor (PDGF) on Ca2+ entry in cultured rat glomerular mesangial cells. In cell-attached patches, application of 50 ng/ml PDGF-BB inside, but not outside, the pipette frequently induced channel openings. The unitary conductance was 0.67 +/- 0.09 pS (n = 8) with 110 mM Mn2+ and 1.03 +/- 0.19 pS (n = 11) with 110 mM Ca2+ as the charge carrier. Number of channels times open probability was 0.515 +/- 0.144 (n = 14) with intrapipette PDGF and 0.037 +/- 0.022 (n = 12) without. Channel kinetics were only slightly voltage dependent. There was no effect of replacing chloride with gluconate in excised inside-out patches, showing that the channel was cation selective. The permeability (P) ratio for P-Mn/P-Na was 1.65 and for P-Ca/P-Na was 1.24. With the use of amphotericin B ''perforated'' whole cell patches, PDGF induced a small inward current (-16.1 +/- 4.33 pA; n = 11, membrane potential = -70 mV) consistent 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 when applied in close proximity to the channel. 2) Once activated, open probability is only slightly voltage dependent. 3) Under normal circumstances, the channel would probably appear to be cation nonselective, but with a permeability tb divalent more than monovalent cations. 4) This PDGF-induced channel could provide a ligand-gated pathway for Ca2+ entry into mesangial cells that does not require membrane depolarization.