The aging heart: changes in the pharmacodynamic electrophysiological response to verapamil in aged rabbit hearts

• Autorzy: Salameh A. , Dhein S. , Fleischmann B. , Grohe C. , Hescheler J. , Linz K.W. , Meyer R.
• Języki publikacji: EN

Abstrakty

EN

The aim of this study was to investigate whether the L-type calcium current (ICa.L) may be altered in aged hearts and whether the classical calcium antagonist verapamil may exhibit altered pharmacological profile in aged hearts. We examined male New Zealand rabbits aged either 6 months or 26 months. To examine ICa.L whole-cell patch-clamp technique was performed on isolated cells. Moreover, activation-recovery intervals (ARI) of isolated hearts (Langendorff method) were assessed using an epicardial 256 channel mapping system. We found that the ICa.L density, normalised to the cell volume was significantly reduced (p<0.001). Maximum conductance was also significantly decreased (p=0.01) and steady state inactivation was shifted to more positive potentials in aged hearts (p<0.001). A slightly reduced effect of ß-adrenergic modulation of the ICa.L in aged hearts, and a significantly reduced effect of carbachol on isoprenaline-stimulated ICa.L in aged hearts was observed. L-type 1c subunit, SERCA2-ATPase and the Na+/Ca2+-exchanger expression were neither significantly different in atrial and ventricular tissues nor between young and old animals. Using the mapping system, isolated hearts were exposed to verapamil (0.005, 0.01, 0.02, 0.05 µM/L). While verapamil did not affect ARI in young hearts, in aged hearts ARI was concentration-dependently reduced and the negative inotropic effect of verapamil was significantly attenuated in aged hearts (p<0.05). From these results we conclude that there are distinct alterations in the electrophysiology of ICa.L (reduced maximum conductance, a shift of the steady state inactivation) in the aged heart which may influence the response to verapamil.

Słowa kluczowe

EN

L-type calcium current; activation-recovery interval; aging; calcium; carbachol; cardiac electrophysiology; heart; isoprenaline; patch clamp technique; rabbit; verapamil

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2010
• Tom: 61
• Numer: 2
• Opis fizyczny: p.141-151,fig.,ref.

Twórcy

autor

Salameh A.

• University of Leipzig, Struempellstrasse 39, 04289 Leipzig, Germany

autor

Dhein S.

autor

Fleischmann B.

autor

Grohe C.

autor

Hescheler J.

autor

Linz K.W.

autor

Meyer R.

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