Differential sensitivity of atrial and ventricular K(ATP) channels to metabolic inhibition

The aim is to compare the activation of ATP-sensitive potassium channels (K(ATP) channels) in intact and metabolically impaired atrial and ventricular myocytes. The K(ATP) channel current is measured by whole cell and gramicidin-perforated patch clamp recordings in 164 cultured neonate rat cardiomyo...

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Bibliographic Details
Published in:Cardiovascular research 2003-02, Vol.57 (2), p.468
Main Authors: Poitry, Serge, van Bever, Laurianne, Coppex, Fabrice, Roatti, Angela, Baertschi, Alex J
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - physiology
Animals
Animals, Newborn
Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology
Cells, Cultured
Diazoxide - pharmacology
Dose-Response Relationship, Drug
Drug Synergism
Gramicidin - pharmacology
Heart Atria - cytology
Heart Atria - metabolism
Heart Ventricles - cytology
Heart Ventricles - metabolism
Ion Channel Gating - drug effects
Ionophores - pharmacology
Membrane Potentials - drug effects
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Patch-Clamp Techniques
Potassium Channels - drug effects
Potassium Channels - metabolism
Rats
Vasodilator Agents
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Summary:The aim is to compare the activation of ATP-sensitive potassium channels (K(ATP) channels) in intact and metabolically impaired atrial and ventricular myocytes. The K(ATP) channel current is measured by whole cell and gramicidin-perforated patch clamp recordings in 164 cultured neonate rat cardiomyocytes. In whole cell recordings with 84 micromol/l ADP in pipette, spontaneous activity is significantly higher in atrium than ventricle, and EC(50) for the K(ATP) channel opener diazoxide is 0.13 micromol/l (atrium) versus 3.1 micromol/l (ventricle). With an ATP-regenerating system in pipette, EC(50) for diazoxide is 19.7 micromol/l (atrium) versus 54.9 micromol/l (ventricle). In gramicidin-perforated patch recordings, atrial myocytes respond significantly to 100 nmol/l of the mitochondrial protonophore CCCP, while ventricular myocytes do not. EC(50) for diazoxide is 129 micromol/l (atrium) versus >2500 micromol/l (ventricle) for myocytes exposed to CCCP, and 676 versus >2500 micromol/l, respectively, without CCCP. (1) K(ATP) channels are significantly more sensitive to metabolic inhibition in atrial than ventricular myocytes. (2) Sensitivity of atrium versus ventricle to the channel opener diazoxide increases from 3:1 to > or = 24:1 with ADP or metabolic inhibition. If extended to intact hearts, the results would predict a higher atrial sensitivity to ischemia, and a high sensitivity of the ischemic atrium to K(ATP) channel openers.
ISSN:0008-6363