Differential sensitivity of atrial and ventricular K(ATP) channels to metabolic inhibition.
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.
Poitry
Serge
S
Department of Physiology, Centre Médical Universitaire, Université de Genève, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.
van Bever
Laurianne
L
Coppex
Fabrice
F
Roatti
Angela
A
Baertschi
Alex J
AJ
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006096:Gramicidin / Q000494:pharmacology; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014665:Vasodilator Agents
D007476:Ionophores; D015221:Potassium Channels; D014665:Vasodilator Agents; D006096:Gramicidin; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D003981:Diazoxide