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In contrast, resistance training mainly stimulates muscle protein synthesis resulting in hypertrophy. The aim of this study was to identify signaling events that may mediate the specific adaptations to these types of exercise. Isolated rat muscles were electrically stimulated with either high frequency (HFS; 6\u00d710 repetitions of 3 s\u2010bursts at 100 Hz to mimic resistance training) or low frequency (LFS; 3 h at 10 Hz to mimic endurance training). HFS significantly increased myofibrillar and sarcoplasmic protein synthesis 3 h after stimulation 5.3\u2010 and 2.7\u2010fold, respectively. LFS had no significant effect on protein synthesis 3 h after stimulation but increased UCP3 mRNA 11.7\u2010fold, whereas HFS had no significant effect on UCP3 mRNA. Only LFS increased AMPK phosphorylation significantly at Thr172 by \u223c2\u2010fold and increased PGC\u20101\u03b1 protein to 1.3 times of control. LFS had no effect on PKB phosphorylation but reduced TSC2 phosphorylation at Thr1462 and deactivated translational regulators. In contrast, HFS acutely increased phosphorylation of PKB at Ser473 5.3\u2010fold and the phosphorylation of TSC2, mTOR, GSK\u20103\u03b2 at PKB\u2010sensitive sites. HFS also caused a prolonged activation of the translational regulators p70 S6k, 4E\u2010BP1, eIF\u20102B, and eEF2. These data suggest that a specific signaling response to LFS is a specific activation of the AMPK\u2010PGC\u20101\u03b1 signaling pathway which may explain some endurance training adaptations. HFS selectively activates the PKB\u2010TSC2\u2010mTOR cascade causing a prolonged activation of translational regulators, which is consistent with increased protein synthesis and muscle growth. We term this behavior the \u201cAMPK\u2010PKB switch.\u201d We hypothesize that the AMPK\u2010PKB switch is a mechanism that partially mediates specific adaptations to endurance and resistance training, respectively.<\/jats:p>","DOI":"10.1096\/fj.04-2179fje","type":"journal-article","created":{"date-parts":[[2005,2,16]],"date-time":"2005-02-16T20:25:37Z","timestamp":1108585537000},"page":"1-23","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":380,"title":["Selective activation of AMPK\u2010PGC\u20101\u03b1 or PKB\u2010TSC2\u2010mTOR signaling can explain specific adaptive responses to endurance or resistance training\u2010like electrical muscle stimulation"],"prefix":"10.1096","volume":"19","author":[{"given":"Philip J.","family":"Atherton","sequence":"first","affiliation":[{"name":"School of Life Sciences University of Dundee  UK"},{"name":"Department of Biological Sciences University of Central Lancashire  UK"},{"name":"Clinical Physiology Laboratory University of Nottingham  UK"}]},{"given":"John A.","family":"Babraj","sequence":"additional","affiliation":[{"name":"School of Life Sciences University of Dundee  UK"}]},{"given":"Kenneth","family":"Smith","sequence":"additional","affiliation":[{"name":"Clinical Physiology Laboratory University of Nottingham  UK"}]},{"given":"Jaipaul","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Central Lancashire  UK"}]},{"given":"Michael J.","family":"Rennie","sequence":"additional","affiliation":[{"name":"Clinical Physiology Laboratory University of Nottingham  UK"}]},{"given":"Henning","family":"Wackerhage","sequence":"additional","affiliation":[{"name":"School of Life Sciences University of Dundee  UK"}]}],"member":"311","published-online":{"date-parts":[[2005,2,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880040204"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00007256-200232080-00002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.91.5.1955"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.90.5.1936"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1123\/ijsnem.11.1.109"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.66.052102.134444"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/386855a0"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/21.1.51"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.266.1.C1"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1242\/jeb.199.4.923","article-title":"Amino-acid-dependent modulation of amino acid transport in Xenopus laevis oocytes","volume":"199","author":"Taylor P. 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