Expression and activity of the glutamate transporter EAAT2 in cardiac hypertrophy: implications for ischaemia reperfusion injury.

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King N, Lin H, McGivan JD, Suleiman MS

Expression and activity of the glutamate transporter EAAT2 in cardiac hypertrophy: implications for ischaemia reperfusion injury.

Pflugers Arch. 2006 Sep;452(6):674-82. Epub 2006 May 23.

PubMed ID

16718509 [ View in PubMed

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Abstract

The expression and activity of the glutamate transporter, excitatory amino acid transporter 2 (EAAT2), in cardiac hypertrophy were investigated with respect to glutamate's potential as a cardioprotective agent. Sarcolemmal vesicles (SV) isolated from hypertrophic hearts of male spontaneously hypertensive rats (SHR) or normotrophic hearts from age-matched male Wistar Kyoto rats (WKY) were used to measure the relative level of EAAT2 expression by Western blotting and the initial rate of 0-0.3 mM L-[(14)C]glutamate uptake. The effects of 20-min global normothermic ischaemia +/-0.5 mM glutamate on cardiac function were measured in isolated working SHR/WKY hearts. In a separate series of hearts, glutamate, lactate and ATP levels were measured. Both the level of EAAT2 expression and the V (max) for sodium-dependent L-[(14)C]glutamate uptake were significantly greater in SHR SV compared to WKY SV. The reperfusion cardiac output (CO) of SHR hearts was significantly worse than that of the WKY hearts (24.3+/-2.2 ml/min vs 39.8+/-3.3 ml/min, n=7/9+/-SE, p<0.01). The addition of 0.5 mM L-glutamate improved the SHR reperfusion CO to 45.2+/-5 ml/min, (n=6+/-SE, p<0.01) but had no effect on WKYs (46.2+/-3.8 ml/min, n=6+/-SE). SHR with 0.5 mM L-glutamate had higher glutamate levels at the start of ischaemia, plus higher glutamate and ATP levels at the end of ischaemia compared to any other group. These results suggest that increased glutamate transporter expression and activity in the SHR hearts helped facilitate glutamate entry into the SHR cardiomyocytes leading to improved myocardial metabolism during ischaemia and better functional recovery on reperfusion.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glutamic acid	Excitatory amino acid transporter 2	Protein	Humans	Unknown	Not Available	Details