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Differential sensitivity of atrial and ventricular KATP channels to metabolic inhibition

Poitry, Serge ; van Bever, Laurianne ; Coppex, Fabrice ; Roatti, Angela ; Baertschi, Alex J.

In: Cardiovascular Research, 2003, vol. 57, no. 2, p. 468-476

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    Titel
    • Differential sensitivity of atrial and ventricular KATP channels to metabolic inhibition
    Autor
    • Poitry, Serge. Department of Physiology, Centre Médical Universitaire, Université de Genève, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland
    • van Bever, Laurianne. Department of Physiology, Centre Médical Universitaire, Université de Genève, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland
    • Coppex, Fabrice. Department of Physiology, Centre Médical Universitaire, Université de Genève, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland
    • Roatti, Angela. Department of Physiology, Centre Médical Universitaire, Université de Genève, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland
    • Baertschi, Alex J.. *Corresponding author. Tel.: +41-22-702-5347; fax: +41-22-702-5402.
    Dokumententyp
    • Postprint
    OAI-PMH-ID
    • oai:doc.rero.ch:293422
    Summary
    Objective: The aim is to compare the activation of ATP-sensitive potassium channels (KATP channels) in intact and metabolically impaired atrial and ventricular myocytes. Methods: The KATP 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 μmol/l ADP in pipette, spontaneous activity is significantly higher in atrium than ventricle, and EC50 for the KATP channel opener diazoxide is 0.13 μmol/l (atrium) versus 3.1 μmol/l (ventricle). With an ATP-regenerating system in pipette, EC50 for diazoxide is 19.7 μmol/l (atrium) versus 54.9 μmol/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. EC50 for diazoxide is 129 μmol/l (atrium) versus <2500 μmol/l (ventricle) for myocytes exposed to CCCP, and 676 versus <2500 μmol/l, respectively, without CCCP. Conclusions: (1) KATP 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 ≥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 KATP channel openers