Age-associated alterations in calcium current and its modulation in cardiac myocytes.
The calcium current is one of the most important components in cardiac excitation-contraction coupling. During aging, the magnitude of L-type Ca++ channel current (ICa,L) is significantly increased in parallel with the enlargement of cardiac myocytes, resulting in unaltered ICa,L density. Since the inactivation of ICa,L is slowed and the action potential duration is prolonged, the net Ca++ influx during each action potential is likely to be increased in senescent hearts relative to young ones. This augmentation of Ca++ influx may be important for the preserved cardiac function of the older heart in the basal state. However, it increases the risk of Ca++ overload and Ca(++)-dependent arrhythmias in the senescent heart. During stress, the response of ICa,L to beta-adrenergic receptor stimulation is markedly reduced, which may be an important cause of the age-related decrease in cardiac reserve function. These age-dependent changes in ICa,L and its modulations are similar to those observed in the enlarged myocytes of the hypertrophied and failing heart.
Zhou
Y Y
YY
Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Lakatta
E G
EG
Xiao
R P
RP
D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015220:Calcium Channels / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D006332:Cardiomegaly / Q000503:physiopathology; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases