The action of isoprenaline on the electrophysiological properties of hypertrophied left ventricular myocytes.
The electrophysiological effects of the beta-agonist, isoprenaline, on hypertrophied left ventricular myocardium were measured to understand better the arrhythmic effects of beta-stimulation on the hypertrophied heart. Left ventricular hypertrophy was induced in guinea-pigs by constriction of the thoracic aorta. An age-matched sham-operated group served as controls. Isolated myocytes were held under voltage- and current clamp and the effect of isoprenaline on the L-type Ca2+ current, I(Ca), a Cl- current, I(Cl), and action potential morphology were measured. Cardiac growth was mirrored by cellular hypertrophy. I(Ca) and I(Cl) current density were reduced as myocyte hypertrophy progressed. The augmentation of I(Ca) and I(Cl) by isoprenaline was also reduced in hypertrophy, but no other characteristics of the two currents, or the dose-dependency of the action of isoprenaline were a function of cardiac growth. Isoprenaline prolonged the action potential, but to a smaller extent in hypertrophied myocytes. This difference in action potential prolongation was abolished by glibenclamide. The changes to I(Ca) and I(Cl) in hypertrophy would not tend to increase triggered activity in this situation. Under maximum inotropic stimulation hypertrophied myocytes show action potential changes which are consistent with intracellular ATP depletion, and which could enhance the likelihood of re-entrant circuits. A simple diffusion model for oxygen is constructed to demonstrate the possibility of cellular hypoxia in hypertrophied myocytes.
Wallis
W
W
The Institute of Urology & Nephrology, University College London, UK.
Cooklin
M
M
Sheridan
D J
DJ
Fry
C H
CH
D000200:Action Potentials / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D018118:Chloride Channels / Q000378:metabolism*; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D018118:Chloride Channels; D015221:Potassium Channels; D007545:Isoproterenol; D005905:Glyburide