The role of a PDGF-activated nonselective cation channel in the proliferative response.
Murine fibroblasts have a 28 pS calcium- and voltage-insensitive NSC that becomes quiescent at G0 arrest and is rapidly and specifically activated by PDGF. Activation is produced by the discrete loss of long channel closures. The NSC can be rapidly and reversibly blocked with the NSAID flufenamic acid, through a prostaglandin-independent mechanism. The cell cycle (not viability) is blocked concomitantly with NSC block. A somatic cell mutant with altered NSC conductance has been isolated and used to clone the genomic locus of the channel. The mutant growth phenotype adds further support to the participation of NSC conductance in cell cycle control.
Gargus
J J
JJ
Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322.
Frace
A M
AM
Jung
F
F
D000818:Animals; D002412:Cations / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002999:Clone Cells; D003360:Cosmids; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015723:Gene Library; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D007739:L Cells; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D016192:Resting Phase, Cell Cycle; D012964:Sodium / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D002412:Cations; D007473:Ion Channels; D010982:Platelet-Derived Growth Factor; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D012964:Sodium; D011188:Potassium