Caffeine stimulates the reverse mode of Na/Ca2+ exchanger in ferret ventricular muscle.
This study investigated the effect of caffeine on the sarcolemmal mechanisms involved in intracellular calcium control. Ferret cardiac preparations were treated with ryanodine and thapsigargin in order to eliminate the sarcoplasmic reticulum (SR) function. This treatment abolished caffeine contracture irreversibly in normal solution. The perfusion with K-free medium that blocked the Na+--K+ pump resulted in a recovery of slow relaxing caffeine contractures similar to Na-free contractures. The amplitude of caffeine contractures was dependent on the bathing [caffeine]o and [Ca2+]o. Divalent cations Ni2+ and Cd2+, which have an inhibitory effect on the Na+/Ca2+ exchanger, produced dose-dependent inhibition of caffeine responses with apparent Ki of 780 +/- 19 and 132 +/- 5 microM, respectively. Caffeine also caused dose-dependent inhibition of Na-free contractures (Ki=4.62 +/- 1.5 mM), and the reduction or removal of [Na+]o exerted an inhibitory effect on caffeine contractures (Ki=73.5 +/- 17.12 mM). These experiments indicate that the increase in resting tension following exposure to caffeine was mediated by Na+/Ca2+ exchanger, which represents an additional element of complexity in caffeine action on cardiac muscle.
Léoty
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Laboratoire de Physiologie Générale, Faculté des Sciences et des Techniques, Nantes, France.
Huchet-Cadiou
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Talon
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Choisy
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Hleihel
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W
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D019831:Sodium-Calcium Exchanger; D012433:Ryanodine; D002110:Caffeine; D019284:Thapsigargin; D011188:Potassium; D002118:Calcium