Inhibition of the voltage-dependent calcium current by extracellular ATP in hamster ventricular cardiomyocytes
| Autor: | Heinrich Kreuzer, Gonska Bd, F. Von zur Muhlen |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.medical_specialty Patch-Clamp Techniques Time Factors Calcium Channels L-Type Physiology G protein Heart Ventricles Adenylate kinase Hamster Guanosine 030204 cardiovascular system & hematology Biology Membrane Potentials 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate 0302 clinical medicine Cricetinae Physiology (medical) Internal medicine medicine Extracellular Animals Patch clamp Egtazic Acid Cells Cultured Chelating Agents 030304 developmental biology 0303 health sciences Mesocricetus Purinergic receptor Heart Adenosine Endocrinology chemistry Biophysics Calcium Channels Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 273:H250-H256 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | The modulation of the high-voltage-activated calcium current (ICa) by external ATP was examined in single ventricular cardiomyocytes of the hamster using the whole-cell configuration of the patch-clamp technique. Extracellular application of ATP (0.1-100 microM) was found to inhibit ICa reversibly. The inhibition followed a slow time course (half time approximately 25 s) and was accompanied by very small changes of the holding current and no shift in the current-voltage relationship. With 100 microM ATP, peak ICa was reduced by approximately 30%. This response was not blocked by the P1 inhibitor 8-cyclopentyl-1,3-dipropylxanthine. The nonhydrolyzable ATP analogs adenosine 5'-O-(3-thiotriphosphate) and AMP-adenosine 5'-[beta,gamma-imido]triphosphate also reduced ICa. The ATP analog alpha,beta-methylene-ATP was about equipotent with ATP at 50 microM. Internal guanosine 5'-O-(3-thiotriphosphate) (200 microM) rendered the ATP-mediated inhibition of ICa poorly reversible, whereas internal guanosine 5'-O-(2-thiodiphosphate) (200-500 microM) had no effect. Holding the intracellular adenosine 3',5'-cyclic monophosphate concentration at a constant high level did not alter the ATP response. We conclude that external ATP inhibits ICa via a P2 purinergic receptor in hamster ventricular myocytes. Our results suggest the involvement of a G protein not coupled to adenylate cyclase. The inhibition of ICa by extracellular ATP might have pathophysiological relevance under conditions of myocardial injury. |
| Databáze: | OpenAIRE |
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