Abstract
Hypertrophied myocytes of failing hearts have prolonged action potential durations. It is unknown how the swelling-activated Cl(-) current (I(Cl,swell)) affects the abnormal AP configuration. We studied I(Cl,swell) in ventricular myocytes isolated from failing and age-matched normal rabbit hearts. We applied whole-cell patch-clamp methodology and activated I(Cl,swell) by lowering tonicity of the superfusate. Neither with ruptured-patch nor with amphotericin B perforated-patch, whole-cell clamp we found I(Cl,swell) active under isotonic conditions in either the normal or the hypertrophied failing heart (HFH) myocytes. I(Cl,swell) caused AP shortening and resting membrane potential (V(m)) depolarization in an osmotic gradient-dependent fashion. However, in the HFH myocytes swelling-induced AP changes were significantly smaller, even though the cells underwent the same relative change in planar cell surface area. Voltage-clamp experiments revealed that in HFH myocytes I(Cl,swell) current density was approximately 50% reduced. Reduced I(Cl,swell) densities in HFH myocytes cause limited AP shortening and V(m) depolarization upon swelling of the cells.
Citations
May 24, 2011·Acta Pharmacologica Sinica·Dayue Darrel Duan
Mar 1, 2006·The Journal of General Physiology·David M Browe, Clive M Baumgarten
Jul 10, 2013·Journal of Cardiovascular Translational Research·Erik BlaauwFrans A van Nieuwenhoven
Aug 10, 2010·Regulatory Peptides·W C De Mello, Y Gerena
Jan 28, 2009·The Journal of Physiology·Dayue Duan
Jul 16, 2011·Journal of Pharmacological Sciences·Shintaro YamamotoTakahiro Iwamoto
May 14, 2004·European Journal of Pharmacology·Lesya M ShubaTerence F McDonald
Nov 7, 2015·Reproductive Sciences·Melissa MarianaIgnacio Verde
Jul 30, 2003·Circulation·Arie O VerkerkE Etienne Verheijck
Jun 21, 2007·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Arie O VerkerkHanno L Tan
Apr 28, 2019·International Journal of Molecular Sciences·Arie O VerkerkRonald Wilders
Jun 11, 2018·Journal of Translational Medicine·Mengmeng LiJiangping Song
Mar 20, 2021·JACC. Clinical Electrophysiology·Lisa A GottliebRuben Coronel
Aug 27, 2021·Frontiers in Cardiovascular Medicine·Daniel TurnerRajan Sah