RT Journal Article
SR Electronic
T1 Subcellular actions and potential adverse cardiac effects of the cardiotonic ionophore monensin.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 567
OP 573
VO 214
IS 3
A1 M Shlafer
A1 P Kane
YR 1980
UL http://jpet.aspetjournals.org/content/214/3/567.abstract
AB Monensin concentrations between 0.5 and 30 microM produced dose-dependent positive inotropy when administered to normal, electrically driven rabbit left atria. These doses did not produce contracture. When monensin was combined with very low concentrations of ouabain (10 or 50 nM), irreversible contracture, irregular responses to electrical stimulation, or both, occurred in a significant number of atria treated with both drugs. This was apparently due to intracellular Na+ overload produced by both drugs, with secondary elevations of intracellular Ca++ concentrations. Monensin (17 nM, 1.7 or 170 microM) did not inhibit canine myocardial Na+mK+-adenosine triphosphatase activity. When administered to mitochondria isolated from normal rabbit hearts, monensin concentrations greater than 10 nM significantly depressed ADP-stimulated (State 3) respiratory rates and calculated respiratory control ratios. Maximum inhibition of the respiratory control ratio (85% decrease) occurred with monensin concentrations of 1 microM or more. These concentrations also significantly decreased calculated ADP:0 ratios. The data show that monensin concentrations required to increase contractility of isolated myocardium can produce marked inhibitory effects on isolated mitochondria, but apparently do not do so when the drug is administered to intact, normal cardiac tissue.