Maladaptation of calcium homoeostasis in aging cardiac myocytes.
With aging, the heart develops myocyte hypertrophy associated with impaired relaxation indices. To define the cellular basis of this adaptation, we examined the physiological changes that arise in calcium handling in the aging heart and contrasted the adaptations that occur following the imposition of a stimulus that alters calcium homeostasis in a young and an old heart. We utilized a cardiac-specific conditional transgenic approach to "switch on" protein kinase (PKC)-beta II expression in mice at different stages of adult life (3 and 12 months) and characterized alterations in ICa and calcium release in wild-type (WT) and PKC-beta II-expressing cells. Amplitude or voltage dependence of ICa were not significantly altered by expression of PKC-beta II at any age. No significant differences in calcium-release properties were seen with age. Upon activation of PKC-beta II, the amplitude of the calcium transient was larger, and the calcium spark frequency was greater in PKC-beta II mice compared to WT at both 3 and 12 months. Spark amplitude increased only in the 12-month PKC-beta II mice. These changes occurred in parallel with an increase in cell size (as determined by capacitance measurements) in the 12-month PKC-beta II mice but not the 3-month PKC-beta II mice. These data suggest that alterations in the calcium-handling machinery of the cardiocyte differ in the context of age and as such may predispose the older heart to the development of a hypertrophic phenotype.
Goldspink
Paul
P
Department of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA.
Ruch
Stuart
S
Los
Tamara
T
Buttrick
Peter
P
García
Jesús
J
D000200:Action Potentials; D000222:Adaptation, Physiological; D000367:Age Factors; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D006332:Cardiomegaly / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D048429:Cell Size; D002478:Cells, Cultured; D006706:Homeostasis; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000473:pathology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta
D011493:Protein Kinase C; D064546:Protein Kinase C beta; D002118:Calcium