Properties of the apamin-sensitive Ca2+-activated K+ channel in PC12 pheochromocytoma cells which hyper-produce the apamin receptor.
Undifferentiated PC12 cell produce high levels of apamin receptors (measured with 125I-apamin) after 7 days in culture. These levels are at least 50 times higher than those found in other cellular types which are also known to have apamin receptors and apamin-sensitive Ca2+-activated K+ channels in their membranes. Treatment of undifferentiated PC12 cells with nerve growth factor maintains these cells in a state having a low level (10 times less after 7 days of culture) of apamin receptors. Ca2+ injection into PC12 cells with the calcium ionophore A23187 has been used to monitor the activity of the Ca2+-activated K+ channel following 86Rb+ efflux. A large component of this Ca2+-activated 86Rb+ efflux is inhibited by apamin. Half-maximum inhibition by apamin of both 86Rb+ efflux and 125I-apamin binding was observed at 240 pM apamin. Another component of 86Rb+ efflux is due to another type of Ca2+-activated K+ channel which is resistant to apamin and sensitive to tetraethylammonium. The Ca2+ channel activator Bay K8644 also triggers an apamin-sensitive Ca2+-dependent 86Rb+ efflux. Bay K8644 has been used to analyze the internal Ca2+ concentration dependence of the apamin-sensitive channel activity. Under normal conditions, the internal Ca2+ concentration is 109 +/- 17 nM, and the apamin-sensitive channel is not activated. The channel is fully activated at an internal Ca2+ concentration of 320 +/- 20 nM.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000818:Animals; D001030:Apamin / Q000378:metabolism / Q000494:pharmacology*; D001514:Bee Venoms / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D010673:Pheochromocytoma / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D012413:Rubidium / Q000378:metabolism
D001514:Bee Venoms; D007473:Ion Channels; D015221:Potassium Channels; D017981:Receptors, Neurotransmitter; C033799:apamin receptor; D001030:Apamin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D012413:Rubidium; D011188:Potassium; D002118:Calcium