A disrupter of actin microfilaments impairs sulfonylurea-inhibitory gating of cardiac K(ATP) channels

P. A. Brady, A. E. Alekseev, L. A. Aleksandrova, L. A. Gomez, Andre Terzic

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

The efficacy with which sulfonylurea drugs inhibit cardiac ATP-sensitive K+ (K(ATP)) channels is reduced during metabolic compromise and cellular contracture. Disruption of the actin microfilament network, which occurs under similar conditions, reduces the sensitivity of the channel toward intracellular ATP. To investigate whether a disrupter of actin microfilaments could also affect the responsiveness of the K(ATP) channel to sulfonylurea drugs, single-channel currents were measured in the inside-out configuration of excised patches from guinea pig ventricular myocytes. Treatment of the internal side of patches with deoxyribonuclease (DNase) I (100 μg/ml), which forms complexes with G actin and prevents actin filament formation, antagonized sulfonylurea-induced inhibition of K(ATP) channels that was coupled with a loss of sensitivity to ATP. The apparent dissociation constant and Hill coefficient for the inhibitory effect of glyburide, a prototype sulfonylurea, on K(ATP)-channel opening were, respectively, 0.13 μM and 0.95 before and 2.7 μM and 0.98 after DNase treatment. DNase did not alter intraburst kinetic properties of the channel. When DNase was denatured or coincubated with purified actin (200 μg/ml), it no longer decreased glyburide-induced channel inhibition. This suggests that sulfonylurea- inhibitory gating of cardiac K(ATP) channels may also be regulated through a mechanism involving subsarcolemmal actin microfilament networks.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume271
Issue number6 40-6
StatePublished - 1996

Fingerprint

Actin Cytoskeleton
Adenosine Triphosphate
Deoxyribonucleases
Glyburide
Actins
Deoxyribonuclease I
Contracture
Pharmaceutical Preparations
Muscle Cells
Guinea Pigs

Keywords

  • adenosine 5'-triphosphate-sensitive potassium channels
  • cytoskeleton
  • deoxyribonuclease I
  • glyburide
  • heart

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

A disrupter of actin microfilaments impairs sulfonylurea-inhibitory gating of cardiac K(ATP) channels. / Brady, P. A.; Alekseev, A. E.; Aleksandrova, L. A.; Gomez, L. A.; Terzic, Andre.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 271, No. 6 40-6, 1996.

Research output: Contribution to journalArticle

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