Effects of IGF-1 on IK and IK1 Channels via PI3K/Akt Signaling in Neonatal Cardiac Myocytes
Previous studies suggest that sarcolemmal potassium currents play important roles in cardiac hypertrophy. IGF-1 contributes to cardiac hypertrophy via activation of PI3K/Akt signaling. However, the relationships between IGF-1, PI3K/Akt signaling and sarcolemmal potassium currents remain unknown. The...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2012/712153 |
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| author | Richard M. Millis Zikiar V. Alvin Aiqiu Zhao Georges E. Haddad |
| author_facet | Richard M. Millis Zikiar V. Alvin Aiqiu Zhao Georges E. Haddad |
| author_sort | Richard M. Millis |
| collection | DOAJ |
| description | Previous studies suggest that sarcolemmal potassium currents play important roles in cardiac hypertrophy. IGF-1 contributes to cardiac hypertrophy via activation of PI3K/Akt signaling. However, the relationships between IGF-1, PI3K/Akt signaling and sarcolemmal potassium currents remain unknown. Therefore, we tested the hypothesis that IGF-1 and PI3K/Akt signaling, independently, decrease sarcolemmal potassium currents in cardiac myocytes of neonatal rats. We compared the delayed outward rectifier (IK) and the inward rectifier (IK) current densities resulting from IGF-1 treatments to those resulting from simulation of PI3K/Akt signaling using adenoviral (Ad) BD110 and wild-type Akt and to those resulting from inhibition of PI3K signaling by LY294002. Ad.BD110 and Ad.Akt decreased IK and these decrements were attenuated by LY 294002. The IGF-1 treatments decreased both IK and IK1 but only the IK decrement was attenuated by LY294002. These findings demonstrate that IGF-1 may contribute to cardiac hypertrophy by PI3K/Akt signal transduction mechanisms in neonatal rat cardiomyocytes. Failure of LY294002 to effectively antagonize IGF-1 induced decrements in IK1 suggests that a signal pathway adjunct to PI3K/Akt contributes to IGF-1 protection against arrhythmogenesis in these myocytes. Our findings imply that sarcolemmal outward and inward rectifier potassium channels are substrates for IGF-1/PI3K/Akt signal transduction molecules. |
| format | Article |
| id | doaj-art-d5f9e0bad67f4565ad7313cf1da8c48b |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-d5f9e0bad67f4565ad7313cf1da8c48b2025-02-03T01:27:38ZengWileyInternational Journal of Cell Biology1687-88761687-88842012-01-01201210.1155/2012/712153712153Effects of IGF-1 on IK and IK1 Channels via PI3K/Akt Signaling in Neonatal Cardiac MyocytesRichard M. Millis0Zikiar V. Alvin1Aiqiu Zhao2Georges E. Haddad3Department of Physiology & Biophysics, College of Medicine, Howard University, Washington, DC 20059, USADepartment of Physiology & Biophysics, College of Medicine, Howard University, Washington, DC 20059, USADepartment of Physiology & Biophysics, College of Medicine, Howard University, Washington, DC 20059, USADepartment of Physiology & Biophysics, College of Medicine, Howard University, Washington, DC 20059, USAPrevious studies suggest that sarcolemmal potassium currents play important roles in cardiac hypertrophy. IGF-1 contributes to cardiac hypertrophy via activation of PI3K/Akt signaling. However, the relationships between IGF-1, PI3K/Akt signaling and sarcolemmal potassium currents remain unknown. Therefore, we tested the hypothesis that IGF-1 and PI3K/Akt signaling, independently, decrease sarcolemmal potassium currents in cardiac myocytes of neonatal rats. We compared the delayed outward rectifier (IK) and the inward rectifier (IK) current densities resulting from IGF-1 treatments to those resulting from simulation of PI3K/Akt signaling using adenoviral (Ad) BD110 and wild-type Akt and to those resulting from inhibition of PI3K signaling by LY294002. Ad.BD110 and Ad.Akt decreased IK and these decrements were attenuated by LY 294002. The IGF-1 treatments decreased both IK and IK1 but only the IK decrement was attenuated by LY294002. These findings demonstrate that IGF-1 may contribute to cardiac hypertrophy by PI3K/Akt signal transduction mechanisms in neonatal rat cardiomyocytes. Failure of LY294002 to effectively antagonize IGF-1 induced decrements in IK1 suggests that a signal pathway adjunct to PI3K/Akt contributes to IGF-1 protection against arrhythmogenesis in these myocytes. Our findings imply that sarcolemmal outward and inward rectifier potassium channels are substrates for IGF-1/PI3K/Akt signal transduction molecules.http://dx.doi.org/10.1155/2012/712153 |
| spellingShingle | Richard M. Millis Zikiar V. Alvin Aiqiu Zhao Georges E. Haddad Effects of IGF-1 on IK and IK1 Channels via PI3K/Akt Signaling in Neonatal Cardiac Myocytes International Journal of Cell Biology |
| title | Effects of IGF-1 on IK and IK1 Channels via PI3K/Akt Signaling in Neonatal Cardiac Myocytes |
| title_full | Effects of IGF-1 on IK and IK1 Channels via PI3K/Akt Signaling in Neonatal Cardiac Myocytes |
| title_fullStr | Effects of IGF-1 on IK and IK1 Channels via PI3K/Akt Signaling in Neonatal Cardiac Myocytes |
| title_full_unstemmed | Effects of IGF-1 on IK and IK1 Channels via PI3K/Akt Signaling in Neonatal Cardiac Myocytes |
| title_short | Effects of IGF-1 on IK and IK1 Channels via PI3K/Akt Signaling in Neonatal Cardiac Myocytes |
| title_sort | effects of igf 1 on ik and ik1 channels via pi3k akt signaling in neonatal cardiac myocytes |
| url | http://dx.doi.org/10.1155/2012/712153 |
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