Regulation of L-type inward calcium channel activity by captopril and angiotensin II via the phosphatidyl inositol 3-kinase pathway in cardiomyocytes from volume-overload hypertrophied rat hearts.

Abstract

Heart failure can be caused by pro-hypertrophic humoral factors such as angiotensin II (Ang II), which regulates protein kinase activities. The intermingled responses of these kinases lead to the early compensated cardiac hypertrophy, but later to the uncompensated phase of heart failure. We have shown that although beneficial, cardiac hypertrophy is associated with modifications in ion channels that are mainly mediated through mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3K) activation. This study evaluates the control of L-type Ca(2+) current (I(Ca,L)) by the Ang II/PI3K pathway in hypertrophied ventricular myocytes from volume-overload rats using the perforated patch-clamp technique. To assess activation of the I(Ca,L) in cardiomyocytes, voltages of 350 ms in 10 mV increments from a holding potential of -85 mV were applied to cardiocytes, with a pre-pulse to -45 mV for 300 ms. Volume overload-induced hypertrophy reduces I(Ca,L), whereas addition of Ang II alleviates the hypertrophic-induced decrease in a PI3K-dependent manner. Acute administration of Ang II (10(-6) mol/L) to normal adult cardiomyocytes had no effect; however, captopril reduced their basal I(Ca,L). In parallel, captopril regressed the hypertrophy and inverted the Ang II effect on I(Ca,L) seemingly through a PI3K upstream effector. Thus, it seems that regression of cardiac hypertrophy by captopril improved I(Ca,L) partly through PI3K.

• Authors: Zikiar Alvin, Graham G Laurence, Bernell R Coleman, Aiqiu Zhao, Majd Hajj-Moussa, Georges E Haddad
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 89 Issue 3 Pg. 206-15 (Mar 2011) ISSN: 1205-7541 [Electronic] Canada
• PMID: 21423294 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channels, L-Type
• Phosphoinositide-3 Kinase Inhibitors
• Angiotensin II
• Captopril
• Phosphatidylinositol 3-Kinase

Topics

• Angiotensin II (pharmacology, therapeutic use)
• Animals
• Calcium Channels, L-Type (physiology)
• Captopril (pharmacology, therapeutic use)
• Cardiomegaly (drug therapy, enzymology)
• Male
• Myocytes, Cardiac (drug effects, enzymology, metabolism)
• Phosphatidylinositol 3-Kinase (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects, physiology)