title: Increase of cGMP and accumulation of 45Ca2+ evoked by drugs acting on sodium or potassium channels.
abstract: Cyclic guanosine monophosphate (cGMP) and 45Ca2+ accumulation were measured in mouse cerebellar slices after treatment with compounds known to affect ion channels in excitable membranes. Scorpion toxin and sea anemone toxin II raise cGMP and 45Ca2+ contents. Both toxins are known to keep the activated sodium channel open. 4-Aminopyridine and tetraethylammonium, which block potassium conductance, also increase cGMP and promote dose-dependently the 45Ca2+ accumulation. The effects of these 4 drugs but not the effects of depolarizing K+-concentrations on the accumulation of cGMP and 45Ca2+ are inhibited by tetrodotoxin. The cyclic GMP content of non-excitable cells, such as isolated hepatocytes from rat and guinea pig, is not affected in a comparable manner. We conclude that in excitable cells, sodium influx triggers an increase of intracellular free calcium and in that way a rise of cGMP. This effect is independent of the ion channel primarily affected. Conversely, the concentration of cGMP might serve as an indicator of intracellular free calcium.
mesh_terms: D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D051379:Mice; D011188:Potassium / Q000378:metabolism*; D012604:Scorpion Venoms / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000631:Aminopyridines; D007473:Ion Channels; D012604:Scorpion Venoms; D013779:Tetrodotoxin; D012964:Sodium; D015761:4-Aminopyridine; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium