Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 287, Issue 3, Pages H1096-H1103Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00079.2004
Keywords
cardiac failure; contraction; isoproterenol; purines; adenine nucleotide
Funding
- NHLBI NIH HHS [HL-48225, HL-28556] Funding Source: Medline
Ask authors/readers for more resources
The P2X(4) purinergic receptor (P2X(4)R) is a ligandgated ion channel. Its activation by extracellular ATP results in Ca2+ influx. Transgenic cardiac overexpression of the human P2X(4) receptor showed an in vitro phenotype of enhanced basal contractility. The objective here was to determine the in vivo cardiac physiological role of this receptor. Specifically, we tested the hypothesis that this receptor plays an important role in modulating heart failure progression. Transgenic cardiac overexpression of canine calsequestrin (CSQ) showed hypertrophy, heart failure, and premature death. Crossing the P2X(4)R mouse with the CSQ mouse more than doubled the lifespan ( 182 +/- 91 days for the binary CSQ/P2X(4)R mouse, n = 35) of the CSQ mouse (71.3 +/- 25.4 days, n = 50, P < 0.0001). The prolonged survival in the binary CSQ/P2X(4)R mouse was associated with an improved left ventricular weight-to-body weight ratio and a restored beta-adrenergic responsiveness. The beneficial phenotype of the binary mouse was not associated with any downregulation of the CSQ level but correlated with improved left ventricular developed pressure and +/- dP/dt. The enhanced cardiac performance was manifested in young binary animals and persisted in older animals. The increased contractility likely underlies the survival benefit from P2X(4) receptor overexpression. An increased expression or activation of this receptor may represent a new approach in the therapy of heart failure.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available