Kirichok Y. New pharmacological effects on potassium channel in hippocampal pyramidal neurons: selective blockage of delayed rectifier channels

A new neuroprotective substance BIIA388Cl was examined for its action on K+ currents in acutely isolated rat hippocampal neurons using the patch-clamp/concentration clamp techniques in the whole-cell configuration. The delayed rectifier K+-current (IDR) was strongly inhibited by externally applied BIIA388Cl, while the transient A-current (IA) remained virtually unaffected. The dose-response relationship for the blocking action of BIIA388Cl revealed the IC50 value of 120 nM. The blocking action of BIIA388Cl on IA was at least 200 times less potent (IC50 = 40mМ). These data allow to conclude that BIIA388Cl is an effective and selective IDR blocker which preferentially binds to activated and inactivated IDR channel. We also demonstrated that nimodipine and nifedipine, which are known as the blockers of L-type calcium channels, suppress IDR in hippocampal pyramidal neurons. The dose-response relationships for the blocking actions of nimodipine and nifedipine revealed the IC50 values of 2.0 ± 0.2 mМ и 44 ± 1 mМ correspondingly.