INHIBITORY EFFECTS OF DIHYDROPYRIDINES ON MACROSCOPIC K+ CURRENTS AND ON THE LARGE-CONDUCTANCE CA2+-ACTIVATED K+ CHANNEL IN CULTURED CEREBELLAR GRANULE CELLS

In cultured cerebellar granule cells, we examined the effects of dihydropyridines (DHPs) on K+ currents, using the whole-cell recording configuration of the patch-clamp technique and on Ca2+-activated K+ channels (''maxi K+ channels'') using outside-out patches. We found that micromolar concentrations of nicardipine, nifedipine, (+) and (-) BAY K 8644, nitrendipine, nisoldipine and (-) nimodipine block 10-60% of macroscopic K+ currents. The most potent of these DHPs was nicardipine and the least potent, (-) BAY K 8644. (+) Nimodipine had no effect on this current. The inhibitory effects of nifedipine and nicardipine were not additive with those of 1 mM tetraethylammonium (TEA). Outside-out recordings of ''maxi K+ channels'' showed a main conductance of 200 pS (in 77% of the patches) and two subconductance states (in 23% of the patches). Neither nifedipine nor nicardipine affected the main conductance, but decreased the values of the subconductance levels. In 10% of these patches, nicardipine induced a flickering activity of the channel. These findings show that both Ca2+ and K+ channels have DHP-sensitive sites, suggesting similarity in electrostatic binding properties of these channels. Furthermore, cerebellar granule cells may express different subtypes of ''maxi K+ channels'' having different sensitivities to DHPs. These drugs may provide new tools for the molecular study of K+ channels.