title: C1q induces chemotaxis and K+ conductance activation coupled to increased cytosolic Ca2+ in mouse fibroblasts.
abstract: Cultured mouse fibroblasts (L cells) respond to whole C with a slow hyperpolarization. Among the C components tested, C1q was found to be most effective. In contrast, the cell did not respond to C1, in which the collagen-like region of the C1q molecule is masked. The C1q-induced hyperpolarizing response was inhibited by collagen or C1q-specific antisera. Human diploid skin fibroblasts (Flow 1,000 cells) also exhibited similar membrane potential changes in response to whole C or C1q. After repeated applications of C1q, the cell membrane became unresponsive (desensitized). The treatment of L cells with pronase E inhibited the C1q-induced response, whereas the response to ATP, which is known to interact to its own receptor, was still preserved. The reversal potential of C responses was close to the K+ equilibrium potential. The hyperpolarizing response was inhibited by a blocker of Ca2+-activated K+ channels in fibroblasts (quinine), by deprivation of extracellular Ca2+ or by a Ca2+ channel blocker (nifedipine). By means of Ca2+-selective microelectrodes, the cytosolic free Ca2+ concentration was found to increase from 126 to 206 nM upon stimulation of L cells with C1q. Using an agarose-well method, L cells were observed to migrate predominantly toward C1q or whole C. It is concluded that the fibroblasts have the C1q receptor sensitive to pronase E and that activation of C1q receptors gives rise to Ca2+ influx, triggering an increase in the cytosolic free Ca2+ ions, which in turn induces a hyperpolarizing response as a result of the stimulation of Ca2+-activated K+ channels and initiates chemotaxis to C1q.
authors.affiliation: Department of Physiology, Kyoto University Faculty of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Oiki
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002633:Chemotaxis; D003166:Complement Activating Enzymes / Q000378:metabolism / Q000502:physiology*; D003172:Complement C1 / Q000378:metabolism / Q000502:physiology*; D015922:Complement C1q; D003165:Complement System Proteins / Q000502:physiology; D003600:Cytosol / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D018960:Hyaluronan Receptors; D007424:Intracellular Fluid / Q000378:metabolism; D007739:L Cells; D008562:Membrane Glycoproteins; D008564:Membrane Potentials; D051379:Mice; D024101:Mitochondrial Proteins; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D011951:Receptors, Complement / Q000502:physiology
chemical_list: C490193:C1qbp protein, mouse; D003172:Complement C1; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D015221:Potassium Channels; D011951:Receptors, Complement; C032402:complement 1q receptor; D015922:Complement C1q; D003165:Complement System Proteins; D003166:Complement Activating Enzymes; D011188:Potassium; D002118:Calcium