Low-affinity block of cardiac K(+) currents by nifedipine.
Nifedipine inhibits a variety of K(+) currents with IC(50) between 4 and 40 microM. 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 < or =10 microM nifedipine, but inhibited by higher concentrations; IC(50) values were 260 microM for I(K1), 275 microM for I(Kr), and 360 microM 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.
Zhabyeyev
P
P
Department of Physiology and Biophysics, Dalhousie University, B3H 4H7, Halifax, Nova Scotia, Canada.
Missan
S
S
Jones
S E
SE
McDonald
T F
TF
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D016276:Ventricular Function
D002121:Calcium Channel Blockers; D015221:Potassium Channels; D009543:Nifedipine