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Regulation of IK by Captopril and ANG II via PI3K pathway in Hypertrophied Cardiac Myocytes
Author(s) -
Alvin Zikiar,
Zhao Aiqiu,
Laurence Graham G.,
Coleman Bernell R.,
Haddad Georges E.
Publication year - 2010
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.24.1_supplement.lb538
Subject(s) - captopril , medicine , endocrinology , myocyte , muscle hypertrophy , angiotensin ii , patch clamp , heart failure , pressure overload , chemistry , cardiac hypertrophy , electrophysiology , blood pressure
Early hypertrophy may be beneficial but sustained hypertrophic activation leads to myocardial dysfunction. Regulation of the repolarizing currents (I K and I K1 ) can be modulated by the activation of humoral factors, such angiotensin II (ANG II), which modulates protein kinases whose integrated responses leads to the early beneficial cardiac hypertrophy and later to heart failure. We have previously found that compensated cardiac hypertrophy is associated with alterations in K + and Ca 2+ channels are mainly mediated through MAP kinase and PI 3‐kinase activation. The aim of this work is to assess the regulation of I K by ANG II/PI3 K pathway in volume overload rat ventricular myocytes, using patch‐clamp in whole‐cell configuration. Cells were stimulated from holding potential of −80mV, by 500msec, 10‐mV step voltages between −120mV +40mV. Cardiomyocytes from 3‐weeks‐shunted animals showed a significant reduction in I K current‐density. Treatment with captopril (0.5g/L/day in drinking water for 3 weeks) alleviated this difference seen between sham and shunt cardiomyocytes. Acute administration of ANG II (10 −6 M) to adult cardiomyocytes treated with captopril similarly reduced the I K current density in shams and shunts. Thus we conclude that captopril enhances I K current density and response to ANG II in hypertrophied myocytes of volume overload shunted rats.