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Cardiac‐specific overexpression of P2X4 receptors enhanced myocyte contractility in the calsequestrin (CSQ) model of cardiomyopathy
Author(s) -
Shen JianBing,
Shutt Robin H,
Pappano Achilles J,
Liang Bruce T
Publication year - 2008
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.22.1_supplement.1130.2
Subject(s) - contractility , myocyte , medicine , cardiomyopathy , cardiac myocyte , calsequestrin , endocrinology , basal (medicine) , ryanodine receptor , contraction (grammar) , heart failure , receptor , insulin
Overexpression of the human P2X 4 purinoceptor (P2X 4 R) rescues the heart failure phenotype in the calsequestrin(CSQ)‐overexpressing transgenic (TG) model of cardiomyopathy (Am J Physiol 287:H1096, 2004). The objective is to study the contractility of binary P2X 4 R/CSQ (Binary) TG myocyte by comparing contraction shortening (CS) in ventricular myocytes. Cell length (102±1.8 μm vs. 108±2.3 μm, SE) and basal CS (5.3%±0.45% vs. 5.4%±0.38% of cell length, SE) at 0.2Hz pacing (22ºC) were similar in WT (N=41) vs. P2X 4 R myocytes (N=59). Cell length in Binary (151±1.6μm, N=54) was shorter than that in CSQ (158±2.1μm, N=60, p<0.05), indicating less hypertrophy. Basal CS in Binary (4.1±0.23 %) was greater than that in CSQ (2.6±0.20 %, p<0.02). At 2.0 Hz, basal CS was also greater in Binary (2.0±0.14%, N=30) than in CSQ (0.9±0.11 %, N=23, P<0.05) cells. With 3μM 2me‐SATP, CS increased significantly in myocytes from all four genotypes but the CS increases in P2X 4 R and Binary TG cells were greater than those in WT and CSQ cells respectively (P<0.05). Conclusion: Overexpression of the P2X 4 R in the CSQ model of cardiomyopathy caused enhanced myocyte contractility to agonist as well as increased basal myocyte contractility; the latter may be due to activation of the overexpressed P2X 4 R by endogenous extracellular ATP in vivo. Enhanced contractility may mediate the heart failure rescuing effect of P2X 4 R overexpression.