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The p 42/44 mitogen‐activated protein kinase inhibitor PD 98059, but not U 0126, increases a K + current in cardiomyocytes
Author(s) -
Aimond F,
Fauconnier J,
Donadille D,
Vassort G
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2003.03826.x
Subject(s) - intracellular , patch clamp , mapk/erk pathway , protein kinase a , arachidonic acid , protein kinase c , kinase , signal transduction , cytosol , chemistry , pharmacology , microbiology and biotechnology , biophysics , biochemistry , enzyme , biology , receptor
Summary 1. The effects of the mitogen‐activated protein kinase (MAPK) inhibitors PD 98059 and U 0126, useful tools to investigate MAPK involvement in intracellular signal transduction pathways, were assessed on cardiomyocytes. 2. In rat freshly isolated ventricular myocytes, under current‐clamp conditions, PD 98059 (40 µmol/L) shortened the action potential. Under whole‐cell patch‐clamp, this compound slowly induced a fast activating sustained outward K + current that was sensitive to 1 mmol/L Ba 2+ , 100 µmol/L Gd 3+ , 3 mmol/L 4‐aminopyridine and 100 µmol/L tetracain. The PD 98059‐induced current was prevented by 40 µmol/L AACOCF 3 , a cytosolic phospholipase A 2 inhibitor. 3. U 0126 (1 µmol/L), a recently developed highly potent p 42/44 MAPK inhibitor, did not alter K + currents. 4. PD 98059, but not U 0126, increased arachidonic acid content, probably as a consequence of its reported cyclo‐oxygenase inhibitory effect. 5. These observations indicate that PD 98059 activates a TREK‐1 like current. Thus, this MAPK inhibitor has to be used with caution because alterations in cell metabolism can be secondary to changes in electrophysiological behaviour.