Hypertrophied ventricular myocytes from failing rabbit hearts have reduced swelling-activated Cl- current densities, which limits action potential shortening during cell swelling.
May alter swelling responses in failing myocytes; hypothesis-generating and requires human validation before clinical consideration.
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. CONCLUSION: Reduced I(Cl,swell) densities in HFH myocytes cause limited AP shortening and V(m) depolarization upon swelling of the cells.
No takes yet. Share an insight, caveat, or question.
Marcel M. G. J. van Borren (2002) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: