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Angiotensin II and IGF‐1 Modulation of Calcium Handling in Compensated Eccentric Cardiac Hypertrophy
Author(s) -
Laurence Graham George,
Whyte Jamal A.,
Alvin Zikiar,
Zhao Aiqiu,
Teos Leyla,
Haddad Georges E.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1448-b
Subject(s) - medicine , endocrinology , calcium , muscle hypertrophy , angiotensin ii , calcium in biology , homeostasis , myocyte , chemistry , endoplasmic reticulum , calcium channel , calcium metabolism , receptor , biochemistry
Given the central role of calcium in excitation‐contraction coupling, changes in calcium homeostasis maybe expected to precede any loss of pump function. Cardiac hypertrophy has been shown to develop as a response to secreted humoral factors such as IGF‐1and ANG II; thus their effect on calcium homeostasis may well be integral to cardiac performance during hypertrophy. The aim was to determine how increased levels of humoral factors present during cardiac hypertrophy affect calcium handling. Using perforated patch clamp techniques and fluorescence microscopy, we assessed the changes in membrane calcium currents and intracellular free calcium concentration in sham and volume‐overload‐induced hypertrophied (3‐week) rat cardiomyocytes with acute administration of IGF‐1 and ANG II. Results indicate that in normal cardiomyocytes, I Ca , L decreased dose dependently when ANG II was administered, whereas IGF‐1 caused a dose dependent increase in I Ca,L . In hypertrophied myocytes, the response of I Ca,L to IGF‐1 (10 −8 M) was significantly increased, while ANG II (10 −6 M) served to augment I Ca,L . Intracellular free calcium responses to ANG II (10‐6 M) in normal myocytes showed dose‐dependent increases, whereas in hypertrophied myocytes there was no significant change in [Ca 2+] i . These data suggest that despite enhanced membrane calcium entry in hypertrophied cardiomyocytes due to ANG II and IGF‐1, release of calcium from the sarcoplasmic reticulum is not correspondingly increased, perhaps revealing a defect in calcium handling during eccentric hypertrophy that may ultimately lead to decreased cardiac performance. Funded by NIH/NIGMS SCORE S06GM08016‐32