Free radicals irreversibly decrease Ca2+ currents in isolated guinea-pig ventricular myocytes. 1995

J S Gill, and W J McKenna, and A J Camm
Department of Cardiological Sciences, St George's Hospital Medical School, London, UK.

The effects of free radicals on voltage-gated Ca2+ currents (ICa) were investigated in single guinea-pig ventricular myocytes using the whole-cell clamp technique. ICa was measured in the baseline state and after the application of free radicals from cumene hydroperoxide or generated from the addition of purine to xanthine oxidase. ICa decreased from 846 +/- 533 (S.D.) pA to 688 +/- 444 pA (n = 7, P < 0.05) in the presence of 100 microM cumene hydroperoxide and from 708 +/- 157 pA to 457 +/- 163 pA (n = 5, P < 0.0001) in the presence of 500 microM cumene hydroperoxide. ICa also decreased from 1303 +/- 560 pA to 965 +/- 360 pA in the presence of the free radical generating system (2.3 mM purine plus 20 U/l xanthine oxidase). The reduced ICa could not be restored by washing for up to 5 min using normal recording solution. We conclude that ICa is decreased in the presence of cumene hydroperoxide and an oxygen-derived free radical generating system in single guinea-pig ventricular myocytes. The cellular Ca2+ overload observed in free radical mediated reperfusion injury is therefore unlikely to result from an increase in sarcolemmal Ca2+ entry via voltage-gated Ca2+ channels.

UI MeSH Term Description Entries
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D011687 Purines A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D005260 Female Females
D005609 Free Radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Free Radical
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006352 Heart Ventricles The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation. Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001555 Benzene Derivatives Organic compounds derived from BENZENE. Derivatives, Benzene
D014969 Xanthine Oxidase An iron-molybdenum flavoprotein containing FLAVIN-ADENINE DINUCLEOTIDE that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. Hypoxanthine Oxidase,Hypoxanthine Dehydrogenase,Hypoxanthine-Xanthine Oxidase,Purine-Xanthine Oxidase,Dehydrogenase, Hypoxanthine,Hypoxanthine Xanthine Oxidase,Oxidase, Hypoxanthine,Oxidase, Hypoxanthine-Xanthine,Oxidase, Purine-Xanthine,Oxidase, Xanthine,Purine Xanthine Oxidase

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