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IGF‐1 Modulatory Effects on I K and I K1 Through ERK1/2 and PI‐3K During Eccentric Cardiac Hypertrophy
Author(s) -
Teos Leyla,
Zhao Aiqiu,
Alvin Zikiar,
Laurence Graham,
Haddad Georges
Publication year - 2007
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.21.6.a1420-d
Subject(s) - medicine , endocrinology , inward rectifier potassium ion channel , muscle hypertrophy , pi3k/akt/mtor pathway , ly294002 , myocyte , patch clamp , protein kinase b , chemistry , biology , ion channel , electrophysiology , microbiology and biotechnology , signal transduction , receptor
The outward rectifier (I K ) and the inward rectifier (I K1 ) K + channels, responsible for the action potential repolarization and maintenance of the resting potential respectively, are altered during cardiac hypertrophy. Activation of insulin‐like growth factor‐1 (IGF‐1) during hypertrophy may affect channel activity. The aim was to study the modulatory effect of IGF‐1 on I K and I K1 through EK1/2 and PI3K pathways during hypertrophy. Using specific inhibitors for ERK1/2 (PD98059) and PI3K/Akt (LY294002), whole‐cell patch‐clamp was conducted on sham and aortocaval shunt‐induced eccentric cardiac hypertrophy myocytes from adult rats. In sham and shunt cardiocytes respectively: ERK1/2 inhibition caused reduction by 33% and 40% in I K density and 38% and 53% in that of I K1 ; Akt inhibition caused decrease by 29% and 23% in I K density and 47% and 17% in that of I K1 . In the presence of LY294002 , IGF‐1 reduced I K density by 36% in sham and 23% in hypertrophied myocytes; whereas it had no effect on I K1 in both groups. In the presence of PD98059, IGF‐1 had no affect on I K or I K1 in sham with slight 7% decrease in shunt. Thus, I K and I K1 are positively modulated by basal ERK and PI3K activities. ERK and PI3K are both sufficient and necessary for I K1 modulation by IGF‐1; whereas only ERK is for I K . Cardiac hypertrophy is associated with a shift towards a larger role of PI3K in the modulation of both K + channel. Supported in part by grants GM08016‐38 NIGMS/NIH and 2G12 RR003048 RCMI, Division of Research Infrastructure, NCRR/NIH.