Purinergic facilitation of ATP-sensitive potassium current in rat ventricular myocytes. 1997

A P Babenko, and G Vassort
INSERM U.390, CHU Arnaud de Villeneuve, Montpellier, France.

1. The effects of different purinergic agonists on the cardiac adenosine 5'-triphosphate (ATP)-sensitive potassium current (IK(ATP)), appearing during dialysis of rat isolated ventricular myocytes with a low-ATP (100 microM) internal solution under whole-cell patch-clamp conditions, were examined in the presence of a P1 purinoceptor antagonist. 2. The extracellular application of ATP in the micromolar range induced, besides known inward currents through cationic and chloride channels, the facilitation of IK(ATP) once IK(ATP) had already been partially activated during the low-ATP dialysis. 3. Analogues of ATP, alpha, beta-methyleneadenosine 5'-triphosphate (alpha, beta meATP), 2-methylthioadenosine triphosphate (2MeSATP), adenosine 5'-O-3-thiotriphosphate (ATP gamma S) similarly facilitated IK(ATP). UTP and ADP were very weak agonists while AMP and adenosine had no detectable effect. 4. The half-maximal stimulating concentration (C50) of alpha, beta meATP, an analogue that did not elicite the interfering inward cationic current was 1.5 microM. Similar apparent C50 (1-2 microM) were observed for ATP and analogues tested with somewhat less maximal effect of ATP gamma S. 5. Suramin, a nonselective P2-purinoceptor antagonist, altered IK(ATP) at the relatively high concentration required to inhibit purinoceptors. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a supposedly predominantly P2x-purinoceptor antagonist, at micromolar concentration inhibited the transient inward current but did not block the facilitation of IK(ATP). 6. Our results demonstrate that ATP and its analogues facilitate IK(ATP) in rat ventricular myocytes by stimulation of non-P1-, non-P2x-purinoceptors.

UI MeSH Term Description Entries
D008297 Male Males
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
D011732 Pyridoxal Phosphate This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE). Pyridoxal 5-Phosphate,Pyridoxal-P,Phosphate, Pyridoxal,Pyridoxal 5 Phosphate,Pyridoxal P
D011983 Receptors, Purinergic Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP. Methyladenine Receptors,Purine Receptors,Purinergic Receptor,Purinergic Receptors,Purinoceptors,Purine Receptor,Purinoceptor,Receptors, Methyladenine,Receptors, Purine,Receptor, Purine,Receptor, Purinergic
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
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
D013498 Suramin A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. Germanin,Moranil,Naganin,Naganol,Naphuride,Suramin Sodium,Suramin, Hexasodium Salt,Suramin, Monosodium Salt,Hexasodium Salt Suramin,Monosodium Salt Suramin,Salt Suramin, Hexasodium,Salt Suramin, Monosodium,Sodium, Suramin

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