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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Reduced I(Cl,swell) densities in HFH myocytes cause limited AP shortening and V(m) depolarization upon swelling of the cells.
van Borren
Marcel M G J
MM
Department of Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. m.m.vanborren@amc.uva.nl
Verkerk
Arie O
AO
Vanharanta
Sakari K
SK
Baartscheer
Antonius
A
Coronel
Ruben
R
Ravesloot
Jan H
JH
D000200:Action Potentials; D000818:Animals; D048429:Cell Size; D018118:Chloride Channels / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D011817:Rabbits
D018118:Chloride Channels; D007552:Isotonic Solutions