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Pivotal Role Of PI3K In Mediating The Inotropic Effects Of Alcohol In Cardiomyocytes
Author(s) -
HADDAD Georges E.,
COUSINS Valerie
Publication year - 2011
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.25.1_supplement.829.6
The beneficial inotropic effects of low ethanol concentration on the heart can become detrimental leading to dilated cardiomyopathy with higher exposures. This crucial shift could be due to ethanol‐activated trophic signaling pathways associated with cardiac inotropy, such as the PI3 kinase (PI3K). The objective is to delineate the pivotal role of PI3K in the ethanol‐induced changes in cardiac inotropy. Sarcomere/cellular contractility and [Ca 2+ ] i measurements were performed (Ionoptix) on adult rat myocytes exposed to low (LA; 1mM), moderate (MA; 10mM) and high (HA; 100mM) ethanol (24h) in the presence or absence of PI3K inhibitor (LY294002; 5uM) or PI3K agonist, IGF‐1 (1uM). LA reduced baseline sarcomeric/cell lengths but increased basal [Ca 2+ ] i , speed of contraction and Ca 2+ release, % shortening, sarcomeric/cellular relaxation and Ca 2+ sequestration times (τ) in PI3K‐dependent manner. Similarly, MA and HA improved % shortening in a PI3K‐dependent manner. But, MA and HA reduced the speed of contraction and prolonged sarcomeric/cellular relaxation and Ca 2+ sequestration independent of PI3K. LA exposure maybe mediating its positive inotropic effects largely through PI3K. However, higher ethanol doses seem to engage additional signaling pathways contributing to their detrimental inotropic effects on the cardiomyocytes. Supported by GM08016‐38 NIGMS/NIH, 2G12 RR003048 RCMI/ NCRR/NIH.