Inhibitory effects of dihydropyridines on macroscopic K+ currents and on the large-conductance Ca(2+)-activated K+ channel in cultured cerebellar granule cells

Pflugers Arch. 1994 Dec;429(2):176-82. doi: 10.1007/BF00374310.

Abstract

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 Ca(2+)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium
  • Cerebellum / cytology
  • Cerebellum / drug effects*
  • Cerebellum / physiology
  • Dihydropyridines / pharmacology*
  • Dose-Response Relationship, Drug
  • Mice
  • Nicardipine / antagonists & inhibitors
  • Potassium Channels / drug effects*
  • Tetraethylammonium Compounds / pharmacology

Substances

  • Dihydropyridines
  • Potassium Channels
  • Tetraethylammonium Compounds
  • Nicardipine
  • Calcium