Activation of single-channel currents in mouse fibroblasts by platelet-derived growth factor.
A nonselective cation channel that we characterized in the mouse L-cell membrane becomes quiescent with serum deprivation (arrested cell growth) and rapidly active upon readdition of serum or, specifically, platelet-derived growth factor (PDGF). Using the patch-clamp technique, we find that the predominant channel in the LMTK- cell line is a bursting nonselective cation channel (the NS channel). In cell-attached and inside-out patches, the channel has a conductance of 28 pS; equal selectivity for Na+, K+, and Cs+; and no anion or divalent cation permeability. The channel open probability is voltage insensitive and in inside-out patches does not correlate with intracellular calcium (0.5 nM to 50 microM). When cultures are rendered quiescent by incubation in serum-free medium, channel open probability is virtually 0 as compared to 0.26 (+/- 0.17) in exponentially growing cultures. If mitogenesis is initiated by readdition of serum to quiescent cells while maintaining cell-attached recording, there is a rapid (15-30 s) activation of the channel (n = 12). The open probability of the patch increases (greater than 0.75) for 2-3 min and then decreases. We have attempted applications of several growth factors (fibroblast-derived growth factor, epidermal growth factor, insulin, bombesin, alpha-thrombin, and vasopressin, individually or in combination) but find that only PDGF (5-100 ng/ml; n = 9) produces channel activation. This activation should provide a Na+ entry pathway parallel to that of the Na/H exchanger.
Frace
A M
AM
Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322.
Gargus
J J
JJ
D000818:Animals; D002414:Cations, Monovalent; D004553:Electric Conductivity; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007739:L Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*
D002414:Cations, Monovalent; D007473:Ion Channels; D010982:Platelet-Derived Growth Factor