Analysis of neurotoxin and mitogen-stimulated sodium transport in human fibroblasts.
Human fibroblasts contain two classes of ouabain-insensitive Na+ channels. One channel is activated by alkaloid neurotoxins in combination with scorpion venom, a response which is similar to that of the voltage-sensitive Na+ ionophore of nerve. The other channel is activated by fetal calf serum, several other mitogenic agents, or low extracellular Ca2+. The nervelike Na+ channel is inhibited by tetrodotoxin but not by amiloride, while the mitogen-stimulated channel is blocked by amiloride but not by tetrodotoxin. The combined effects of neurotoxins and low Ca2+ on Na+ uptake are additive, consistent with the conclusion that these Na+ pathways are different and independent. Studies of Na+ efflux show the presence of two intracellular Na+ compartments. When Na+ flux through the (Na+ + K+)-ATPase pump is inhibited by ouabain, compartment A has a high rate constant of efflux (K1 = 0.30 mn-1) and constitutes 60% of the total cellular Na+. Compartment B, with a markedly smaller efflux constant (k2 = -0.07), contains the remaining 40% of cell Na+. Stimulation of flux through the nervelike channel has a pronounced effect on the rate constants and Na+ content of both compartments (K1 = 0.56, k2 = 0.10), but activation of the mitogenic channel has a pronounced effect only on the rate of efflux from compartment A and on the size of compartment B. A cytoplasmic-nuclear model for the Na+ compartments is presented.
D001496:Batrachotoxins / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008934:Mitogens / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology*; D012604:Scorpion Venoms / Q000494:pharmacology; D012867:Skin; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D001496:Batrachotoxins; D007473:Ion Channels; D008934:Mitogens; D009498:Neurotoxins; D012604:Scorpion Venoms; D013779:Tetrodotoxin; D010042:Ouabain; D014701:Veratridine; D012964:Sodium; D002118:Calcium