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The aim was to examine the modulatory effects of IGF-I on I<jats:sub>K<\/jats:sub> and I<jats:sub>K1<\/jats:sub> through mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways during hypertrophy. With the use of specific inhibitors for ERK1\/2 (PD98059), p38 MAPK (SB203580) and PI3K\/Akt (LY294002), Western blot and whole cell patch-clamp were conducted on sham and aorto-caval shunt-induced hypertrophy adult rat myocytes. Basal activation levels of MAPKs and Akt were increased during hypertrophy. Acute IGF-I (10<jats:sup>\u22128<\/jats:sup> M) enhanced basal activation levels of these kinases in normal hearts but only those of Akt in hypertrophied ones. I<jats:sub>K<\/jats:sub> and I<jats:sub>K1<\/jats:sub> activities were lowered by IGF-I. Inhibition of ERK1\/2, p38 MAPK, or Akt reduced basal I<jats:sub>K<\/jats:sub> activity by 70, 32, or 50%, respectively, in normal cardiomyocytes vs. 53, 34, or 52% in hypertrophied ones. However, basal activity of I<jats:sub>K1<\/jats:sub> was reduced by 45, 48, or 45% in the former vs. 63, 43, or 24% in the latter. The inhibition of either MAPKs or Akt alleviated IGF-I effects on I<jats:sub>K<\/jats:sub> and I<jats:sub>K1<\/jats:sub>. We conclude that basal I<jats:sub>K<\/jats:sub> and I<jats:sub>K1<\/jats:sub> are positively maintained by steady-state Akt and ERK activities. K<jats:sup>+<\/jats:sup> channels seem to be regulated in a dichotomic manner by acutely stimulated MAPKs and Akt. Eccentric cardiac hypertrophy may be associated with a change in the regulation of the steady-state basal activities of K<jats:sup>+<\/jats:sup> channels towards MAPKs, while that of the acute IGF-I-stimulated ones toward Akt. <\/jats:p>","DOI":"10.1152\/ajpheart.321.2008","type":"journal-article","created":{"date-parts":[[2008,8,29]],"date-time":"2008-08-29T20:34:12Z","timestamp":1220042052000},"page":"H1834-H1845","source":"Crossref","is-referenced-by-count":20,"title":["Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy"],"prefix":"10.1152","volume":"295","author":[{"given":"Leyla Y.","family":"Teos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiqiu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zikiar","family":"Alvin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham G.","family":"Laurence","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanfu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georges E.","family":"Haddad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0752277.x"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008192200"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20031940"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108145200"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199306000-00005"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.8.1180"},{"key":"R7","unstructured":"Cobb MH, Ross EM. 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