Low-affinity block of cardiac K + currents by nifedipine

Nifedipine inhibits a variety of K + currents with IC 50 between 4 and 40 μM. Among the more sensitive of these are two types (transient outward and ultrarapid hKv1.5) found in the heart. To evaluate the actions of the drug on other prominent cardiac K + currents, guinea-pig ventricular myocytes wer...

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Bibliographic Details
Published in:European journal of pharmacology 2000-08, Vol.401 (2), p.137-143
Main Authors: Zhabyeyev, Pavel, Missan, Sergiy, Jones, Stephen E., McDonald, Terence F.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Calcium Channel Blockers - pharmacology
Cardiovascular system
delayed-rectifier
Dose-Response Relationship, Drug
Electric Stimulation
Guinea Pigs
guinea-pig
Heart Ventricles - cytology
Heart Ventricles - drug effects
inward-rectifier
K + current
Male
Medical sciences
Membrane Potentials - drug effects
Miscellaneous
Nifedipine
Nifedipine - pharmacology
Pharmacology. Drug treatments
Potassium Channels - drug effects
Potassium Channels - physiology
Time Factors
Ventricular Function
Ventricular myocyte
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Summary:Nifedipine inhibits a variety of K + currents with IC 50 between 4 and 40 μM. Among the more sensitive of these are two types (transient outward and ultrarapid hKv1.5) found in the heart. To evaluate the actions of the drug on other prominent cardiac K + currents, guinea-pig ventricular myocytes were voltage-clamped for measurement of inwardly rectifying K + current ( I K1), rapidly activating delayed-rectifier K + current ( I Kr), and slowly activating delayed-rectifier K + current ( I Ks). The currents were unaffected by ≤10 μM nifedipine, but inhibited by higher concentrations; IC 50 values were 260 μM for I K1, 275 μM for I Kr, and 360 μM for I Ks. The time- and voltage-dependent properties of I Ks were unaffected by the drug, and full block was attained on the first depolarisation after a rest. The results establish that the sensitivity of I Kr and I Ks to inhibition by nifedipine is approximately 50 times lower than the sensitivity of other cardiac delayed-rectifier K + currents.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(00)00413-1