Effects of the Ca-antagonist nicardipine on K+ currents and Na+-Ca2+ exchange in frog atrial fibres.
This paper concerns the specificity of nicardipine, a calcium antagonist from the dihydropyridine class which is used in the treatment of cardiovascular disorders. It is well established that in cardiac cells dihydropyridines inhibit the calcium current (Isi) and the correlated phasic tension. In this study we demonstrate that nicardipine, in the concentration range which blocks Isi (KD = 1 microM) also decreases the amplitude of the potassium-delayed current (KD = 3 microM) in frog atrial fibres. Moreover, tonic tension, which has been reported to be directly dependent on the Na+-Ca2+ exchange, was also reduced by nicardipine and the time course of the onset of both contraction and relaxation was significantly slowed. These results indicate that on depolarized membranes, dihydropyridines probably affect voltage-dependent mechanisms with a high threshold of activation that are unrelated to Ca2+ channels, such as potassium-delayed current and Na+-Ca2+ exchange.
Richard
S
S
Centre de Recherches de Biochimie Macromoléculaire, CNRS LP8402-INSERM U.249, Université de Montpellier I-BP 5051, France.
Charnet
P
P
Ouadid
H
H
Tiaho
F
F
Nargeot
J
J
D000818:Animals; D001001:Anura; D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006321:Heart / Q000502:physiology; D066298:In Vitro Techniques; D007474:Ion Exchange; D009129:Muscle Tonus / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D012964:Sodium / Q000502:physiology*
D015221:Potassium Channels; D012964:Sodium; D009529:Nicardipine; D009543:Nifedipine; D002118:Calcium