Increased sodium ion conductance through nicotinic acetylcholine receptor channels in PC12 cells exposed to nerve growth factors.
22Na+ uptake in response to cholinergic stimulation was measured in PC12 cells grown in media containing either beta-nerve growth factor (NGF) from mouse submaxillary gland or a component of Bungarus multicinctus venom (fraction 9B) which has nerve growth factor activity. Our results showed that each of these nerve growth factors increased the Na+ conductance capacity of ACh receptor-linked ion channels in PC12 cells. Compared to untreated cells, Na+ uptake was enhanced by about 40% in cells exposed for 24 to 30 hr to either 50 ng/ml of beta-NGF or to 5 micrograms/ml of fraction 9B. This cholinergically stimulated Na+ flux increased with time and reached a level 2- to 3-fold higher than that of untreated cells after 4 to 6 days' exposure to NGFs. The generation of neurites in response to NGFs from either source occurred with the same time course as the increase in Na+ channel conductance. Growth factor-enhanced Na+ uptake remained for several days after NGFs were removed from cells and neurites were lost. Na+ flux into untreated and into 9B- or beta-NGF-treated cells was inhibited to a greater extent by a nicotinic than by a muscarinic antagonist. Dibutyryl cyclic AMP did not cause an increase in Na+ uptake in response to cholinergic agonists at concentrations which stimulated neurite-like process formation, and dibutyryl cyclic AMP did not potentiate the effects of NGFs.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
C038824:Bungaris multicinctus venom fraction 9B; D002038:Bungarotoxins; D007473:Ion Channels; D009414:Nerve Growth Factors; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D003994:Bucladesine; D009538:Nicotine; D002217:Carbachol; D012964:Sodium