Faculty Collaboration Database

Inhibition of pinacidil induced IK(ATP) in heart by changes in extracellular pH. Cardiovasc Res 1994 Jun;28(6):836-40

Date

06/01/1994

Pubmed ID

7923288

DOI

10.1093/cvr/28.6.836

Scopus ID

2-s2.0-85047680861 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

OBJECTIVE: The aim was to determine whether extracellular protons influence the activation of ATP sensitive potassium channels (KATP) in heart by the drug pinacidil.

METHODS: Single channel and whole cell currents were measured in enzymatically dispersed guinea pig ventricular myocytes with patch clamp procedures. ATP sensitive potassium channel activity was induced by pinacidil in whole cell experiments and either by lowering cytoplasmic ATP or pinacidil in membrane patch experiments.

RESULTS: Extracellular acidification inhibited and extracellular alkalisation potentiated ATP sensitive potassium channel currents (IK(ATP)) induced by pinacidil under whole cell conditions. In membrane patches, IK(ATP) induced by low cytoplasmic ATP (1 mM) was not sensitive to changes in extracellular pH, but IK(ATP) induced by cytoplasmic application of pinacidil was inhibited by extracellular acidification.

CONCLUSIONS: Interactions between protons and pinacidil drug molecules underlie the pH dependent changes in IK(ATP) induced by pinacidil. Based on the kinetics of pH dependent changes in pinacidil induced channel activity in inside-out membrane patches, our data suggest that the important inhibitory site of action of this drug is located on the extracellular side of the cell membrane.

Author List

Kwok WM, Kass RS

Author

Wai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Animals
Cells, Cultured
Extracellular Space
Female
Guanidines
Guinea Pigs
Hydrogen-Ion Concentration
Male
Membrane Potentials
Myocardium
Pinacidil
Potassium Channels
Protons
Vasodilator Agents