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Pacing Rate Regulates ERK Phosphorylation In Mouse Heart
Author(s) -
Knollmann Bjorn C,
Lo Yaye,
Hliang Thinn,
Suzuki Yuichiro
Publication year - 2006
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.20.5.a1123
Subject(s) - phosphorylation , mapk/erk pathway , ventricle , heart rate , kinase , medicine , heart failure , protein kinase a , endocrinology , chemistry , biology , microbiology and biotechnology , blood pressure
Chronic increases in heart rate via fast pacing can induce heart failure within a few weeks. This phenotype is associated with activation and phosphorylation of several mitogen‐activated protein kinases (MAPK, i.e., p38, JNK, ERK) in the diseased muscle tissue. The time course of MAPK activation remains unknown. Here, we examine the effect of acutely changing the heart rate on ERK phosphorylation in isolated perfused mouse hearts. Methods Hearts were excised, the AV node ablated and retrogradely perfused in the Langendorff’ mode. The effect of heart rate was examined by pacing the left ventricle at 3 different rates: fast (750 b/min), at the intrinsic heart rate of isolated perfused hearts (400 b/min) and slow (200 b/min). Total and phosphorylated ERK (pERK) was quantified by immunoblot. Results After 15 minutes of slow pacing, pERK was increased 1.5‐fold compared to normal pacing (n = 9, p<0.05). The effect was reversible upon switching back to a normal pacing rate. Fast pacing significantly decreased pERK. Levels of pERK reached a maximum 3‐fold increase at 4 min after the onset of slow pacing and then slowly decayed. Conclusion Pacing rate dynamically regulates the level of ERK phosphorylation in mouse ventricular muscle.