Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy
Copyright policy )Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy
The potassium channels IK and IK1, responsible for the action potential repolarization and resting potential respectively, are altered during cardiac hypertrophy. The activation of insulin-like growth factor-I (IGF-I) during hypertrophy may affect channel activity. The aim was to examine the modulatory effects of IGF-I on IK and IK1 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 (10−8 M) enhanced basal activation levels of these kinases in normal hearts but only those of Akt in hypertrophied ones. IK and IK1 activities were lowered by IGF-I. Inhibition of ERK1/2, p38 MAPK, or Akt reduced basal IK activity by 70, 32, or 50%, respectively, in normal cardiomyocytes vs. 53, 34, or 52% in hypertrophied ones. However, basal activity of IK1 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 IK and IK1. We conclude that basal IK and IK1 are positively maintained by steady-state Akt and ERK activities. K+ 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+ channels towards MAPKs, while that of the acute IGF-I-stimulated ones toward Akt.
- Howard University United States
- East Tennessee State University United States
Male, phosphatidylinositol 3-kinase, Potassium Channels, Time Factors, 610, Cardiomegaly, Membrane Potentials, Rats, Sprague-Dawley, Phosphatidylinositol 3-Kinases, Animals, insulin-like growth factor-I, Myocytes, Cardiac, Insulin-Like Growth Factor I, Phosphorylation, Protein Kinase Inhibitors, Phosphoinositide-3 Kinase Inhibitors, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, mitogen activated protein kinase, Rats, Disease Models, Animal, Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, Signal Transduction
Male, phosphatidylinositol 3-kinase, Potassium Channels, Time Factors, 610, Cardiomegaly, Membrane Potentials, Rats, Sprague-Dawley, Phosphatidylinositol 3-Kinases, Animals, insulin-like growth factor-I, Myocytes, Cardiac, Insulin-Like Growth Factor I, Phosphorylation, Protein Kinase Inhibitors, Phosphoinositide-3 Kinase Inhibitors, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, mitogen activated protein kinase, Rats, Disease Models, Animal, Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, Signal Transduction
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