The effects of isoproterenol on abnormal electrical and contractile activity and diastolic calcium are attenuated in myocytes from aged Fischer 344 rats.
We investigated whether the age-related decrease in sensitivity of the heart to catecholamines was accompanied by changes in Ca(2+) homeostasis and abnormal electrical and contractile activity caused by beta-adrenergic receptor (beta-AR) stimulation. Ventricular myocytes were isolated from young adult (3 months) and aged (24 months) male Fischer 344 rats. Unloaded cell shortening was measured in field-stimulated myocytes (2Hz, 37 degrees C); membrane currents and action potentials were measured with microelectrodes. Contractile responses to the non-selective beta-AR agonist, isoproterenol were significantly decreased in aged myocytes compared to younger myocytes and aged myocytes were less sensitive to isoproterenol. In contrast, Ca(2+) transients measured simultaneously with contractions were similar between groups. Isoproterenol increased sarcoplasmic reticulum Ca(2+) stores in both groups, but the increase was larger in aged cells. However, signs of Ca(2+) overload induced by isoproterenol were reduced with age. Diastolic Ca(2+) accumulation, contracture and the incidences of transient inward current, oscillatory afterpotentials (OAPs), aftertransients and aftercontractions induced by isoproterenol also were reduced with age. These results demonstrate that aged myocytes exhibit fewer signs of Ca(2+) overload in response to isoproterenol than young adult myocytes. These age-related changes in intracellular Ca(2+) may protect the aging heart against induction of arrhythmias initiated by OAPs.(1).
Farrell
Spring R
SR
Department of Pharmacology, Sir Charles Tupper Medical Building, Dalhousie University, 5850 College St., Halifax, Nova Scotia, Canada B3H 1X5.
Howlett
Susan E
SE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D003971:Diastole / Q000187:drug effects; D004594:Electrophysiology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032342:Muscle Cells / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D002118:Calcium