Increase of cGMP and accumulation of 45Ca2+ evoked by drugs acting on sodium or potassium channels.

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.