Reduced swelling-activated Cl- current densities in hypertrophied ventricular myocytes of rabbits with heart failure

Reduced swelling-activated Cl- current densities in hypertrophied ventricular myocytes of rabbits with heart failure

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. W...

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Bibliographic Details
Published in:Cardiovascular research Vol. 53; no. 4; pp. 869 - 878
Main Authors: VAN BORREN, Marcel M. G. J, VERKERK, Arie O, VANHARANTA, Sakari K, BAARTSCHEER, Antonius, CORONEL, Ruben, RAVESLOOT, Jan H
Format: Journal Article
Language:English
Published: Oxford Oxford University Press 01-03-2002
Subjects:
Action Potentials
Animals
Biological and medical sciences
Cardiology. Vascular system
Cell Size
Chloride Channels - metabolism
Heart
Heart Failure - metabolism
Heart Failure - pathology
Heart Failure - physiopathology
Heart failure, cardiogenic pulmonary edema, cardiac enlargement
Heart Ventricles - cytology
Heart Ventricles - metabolism
Isotonic Solutions - pharmacology
Male
Medical sciences
Membrane Potentials
Osmolar Concentration
Patch-Clamp Techniques
Rabbits
Heart
Heart failure
Pathogenesis
Rabbit
Cardiovascular disease
Ionic channel
Lagomorpha
Myocyte
Vertebrata
Mammalia
Heart disease
Animal
Hypertrophy
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Summary: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.
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ISSN:0008-6363
1755-3245
DOI:10.1016/S0008-6363(01)00507-7