BRL 34915 (cromakalim) enhances voltage-dependent K+ current in cultured rat hippocampal neurons

The whole cell voltage-clamp recording technique was used to study the effects of the benzopyran antihypertensive agent BRL 34915 on voltage-dependent outward currents in cultured rat hippocampal neurons. Extracellular perfusion with BRL 34915 (10-500 microM) produced a dose-dependent increase in the sustained (minimally inactivating) voltage-dependent outward current without altering the transient outward current (IA) or producing a change in the resting current at -60 mV. One-half maximal facilitation of the sustained outward current occurred at 40 microM and maximal facilitation (59%) at 100 microM. The increase in outward current occurred at all potentials where hippocampal neurons exhibited outward rectification (greater than -30 mV). The effect of BRL 34915 was slow to develop (requiring as long as 5-15 min to achieve maximal effect) and persisted for at least 10-15 min after cessation of the drug superfusion. Like the sustained outward current recorded under control conditions, the outward current augmented by BRL 34915 was inhibited by the K+ channel blocker tetraethylammonium (20 mM). These results indicate that BRL 34915 can enhance the activity of sustained voltage-dependent K+ channels in mammalian CNS neurons.