Glyburide-sensitive K+ channels in cultured rat hippocampal neurons: Activation by cromakalim and energy-Depleting conditions

Dora M T Politi, Michael A Rogawski

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Previous studies in our laboratory have shown that cromakalim activates a tetraethylammonium-sensitive K+ current in cultured embryonic rat hippocampal neurons. This phenomenon was further characterized using whole-cell voltage-clamp and single-channel recording techniques. Glyburide (1-25 μM), an antagonist of ATP-sensitive K+ channels, produced a concentration-dependent depression of the cromakalim-activated current. In contrast, charybdotoxin (100 nM), an antagonist of some Ca2+-dependent and other K+ channels, not only failed to block the effect of cromakalim but actually produced a moderate enhance-ment of the cromakalim-activated K+ current. Neither glyburide nor charybdotoxin affected resting or voltage-activated K+ currents in the absence of cromakalim. Exposure of the cells to energy-depleting conditions (0.24 μg/ml oligomycin and 10 mM 2-deoxy-D-glucose) also activated an outward current. Single-channel recordings in the cell-attached configuration showed that cromakalim (100 μM) stimulated the opening of flickery single channels having a unitary conductance of ∼26 pS and a prolonged burst duration (mean open time, ∼131 msec); similar channel openings were observed in patches from cells exposed to energy-depleting conditions. In patches containing a single K+ channel, the open probability in the presence of cromakalim was ∼0.6 and in the presence of energy-depleting conditions was ∼0.8; in the absence of either of these treatments, channel openings were not observed. Glyburide produced a reversible inhibition of the channels activated by cromakalim and energy-depleting conditions. These data provide additional support for the existence of ATP-sensitive K+ channels in central neurons and indicate that the K+ channels whose opening is stimulated by cromakalim are likely to be of the ATP-sensitive type.

Original languageEnglish (US)
Pages (from-to)308-315
Number of pages8
JournalMolecular Pharmacology
Volume40
Issue number2
StatePublished - Aug 1991
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Pharmacology

Cite this