Pentylenetetrazole suppresses the potassium current in Euhadra neurons which is coupled with...

The Ca2+/calmodulin-dependent protein phosphorylation-related mechanism underlying pentylenetetrazole (PTZ)-induced reduction of delayed potassium current (IKD) was examined in identified Euhadra neurons. PTZ gradually reduced peak IKD in a dose-dependent manner, as well as an inhibition of Ca2+/calmodulin-dependent protein phosphorylation. Similar effects were observed by a general protein kinase inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpoperazine, whose saturating dose occluded the action of PTZ on the IKD. Intracellular injection of Ca2+/calmodulin-dependent protein kinase II transiently restored the PTZ-suppressed IKD nearly to the pre-PTZ level, whereas either CaCl2 or calmodulin, injected in the same way, had little effect. However, this restoration was not detectable in the presence of N-(6-aminohexyl)-5-chloronaphthalenesulfonamide, a calmodulin inhibitor, in the perfusate. These results suggest that PTZ suppresses the potassium current coupled with Ca2+/calmodulin-dependent protein phosphorylation.