© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Reduced swelling-activated Cl– current densities in hypertrophied ventricular myocytes of rabbits with heart failure*
aDepartment of Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
bExperimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
* Corresponding author. Tel.: +31-20-566-4670; fax: +31-20-691-9319 m.m.vanborren{at}amc.uva.nl
Objective: Hypertrophied myocytes of failing hearts have prolonged action potential durations. It is unknown how the swelling-activated Cl– current (ICl,swell) affects the abnormal AP configuration. Methods: We studied ICl,swell in ventricular myocytes isolated from failing and age-matched normal rabbit hearts. We applied whole-cell patch-clamp methodology and activated ICl,swell by lowering tonicity of the superfusate. Results: Neither with ruptured-patch nor with amphotericin B perforated-patch, whole-cell clamp we found ICl,swell active under isotonic conditions in either the normal or the hypertrophied failing heart (HFH) myocytes. ICl,swell caused AP shortening and resting membrane potential (Vm) 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 ICl,swell current density was
50% reduced. Conclusion: Reduced ICl,swell densities in HFH myocytes cause limited AP shortening and Vm depolarization upon swelling of the cells.
KEYWORDS Cl-channel; Heart failure; Hypertrophy; Myocytes
* For this manuscript Dr Steve Soroto acted as guest-editor.
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