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Cardiovasc Res ; 57(2): 468-76, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12566119

ABSTRACT

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


Subject(s)
Adenosine Triphosphate/physiology , Myocytes, Cardiac/metabolism , Potassium Channels/metabolism , 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 , Patch-Clamp Techniques , Potassium Channels/drug effects , Rats , Vasodilator Agents
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