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-adrenergic stimulation on ionic
currents of cultured adult guinea pig cardiomyocytes
1 Research Center and Department of Medicine, Montreal Heart Institute, Montreal H1T 1C8, and University of Montreal, Montreal H3C 3J7; and 2 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada
Short-term stimulation of 
-receptors
is known to affect cardiac ion channels; however, the impact of
longer-term stimulation on intrinsic channel function is poorly
understood. To evaluate this, cultured guinea pig ventricular myocytes
were exposed to isoproterenol (10 nM), vehicle, or isoproterenol plus
propranolol (1 µM) for 48 h. Sustained exposure to isoproterenol
decreased the density of the inward rectifier
(IK1), slow delayed rectifier (IKs), and L-type Ca2+
(ICa L) currents, effects that were fully
prevented by propranolol. Changes in K+ currents were
prevented by the 1-selective antagonist CGP-20712A, unaffected by the 2-antagonist ICI-118,551, and mimicked
by the membrane-permeable cAMP analog 8-bromo-cAMP. Isoproterenol did not alter the current-voltage relationship of the K+
currents but increased the density of T-type Ca2+ current
(ICa T) and thereby increased the proportion of the total Ca2+ current at more negative potentials. We
conclude that sustained exposure to isoproterenol reduces
IK1, IKs, and
ICa L density and increases the density of
ICa T. The direct ionic current remodeling
effects of sustained -adrenoceptor stimulation resemble changes
reported with heart failure and may be important in arrhythmogenic ionic remodeling.
ion-channel regulation; cardiac arrhythmias; calcium channels; potassium channels; sympathetic nervous system
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