N-n-Butyl haloperidol iodide inhibits the augmented Na+/Ca2+ exchanger currents and L-type Ca2+ current induced by hypoxia/reoxygenation or H2O2 in cardiomyocytes.

Abstract

N-n-butyl haloperidol iodide (F(2)), a novel quaternary ammonium salt derivative of haloperidol, was reported to antagonize myocardial ischemia/reperfusion injuries. To investigate its mechanisms, we characterized the effects of F(2) on Na(+)/Ca(2+) exchanger currents (I(NCX)) and the L-type Ca(2+) channel current (I(Ca,L)) of cardiomyocytes during either hypoxia/reoxygenation or exposure to H(2)O(2). Using whole-cell patch-clamp techniques, the I(NCX) and I(Ca,L) were recorded from isolated rat ventricular myocytes. Exposure of cardiomyocytes to hypoxia/reoxygenation or H(2)O(2) enhanced the amplitude of the inward and outward of I(NCX) and I(Ca,L). F(2) especially inhibited the outward current of Na(+)/Ca(2+) exchanger, as well as the I(Ca,L), in a concentration-dependent manner. F(2) inhibits cardiomyocyte I(NCX) and I(Ca,L) after exposure to hypoxia/reoxygenation or H(2)O(2) to antagonize myocardial ischemia/reperfusion injury by inhibiting Ca(2+) overload.

• Authors: Yongpan Huang, Fenfei Gao, Yanmei Zhang, Yicun Chen, Bin Wang, Yanshan Zheng, Ganggang Shi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 421 Issue 1 Pg. 86-90 (Apr 27 2012) ISSN: 1090-2104 [Electronic] United States
• PMID: 22487792 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Calcium Channels, L-Type
• N-n-butyl haloperidol iodide
• Sodium-Calcium Exchanger
• Hydrogen Peroxide
• Haloperidol

Topics

• Animals
• Calcium Channels, L-Type (metabolism)
• Cell Hypoxia
• Haloperidol (analogs & derivatives, pharmacology)
• Hydrogen Peroxide (pharmacology)
• Male
• Myocardial Reperfusion Injury (metabolism)
• Myocytes, Cardiac (drug effects, metabolism)
• Patch-Clamp Techniques
• Rats
• Rats, Sprague-Dawley
• Sodium-Calcium Exchanger (antagonists & inhibitors, metabolism)