Effects of carvedilol on transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes.
Carvedilol is a beta- and alpha(1)-adrenoceptor antagonist. It is widely used in the treatment of cardiovascular diseases including atrial arrhythmias. However, it is unclear whether carvedilol may affect the repolarization currents, transient outward K(+) current (I(to)) and ultra-rapid delayed rectifier K(+) current (I(Kur)) in the human atrium. The present study evaluated effects of carvedilol on I(to) and I(Kur) in isolated human atrial myocytes by whole-cell patch-clamp recording technique. We found that carvedilol reversibly inhibited I(to) and I(Kur) in a concentration-dependent manner. Carvedilol (0.3 microM) suppressed I(to) from 9.2+/-0.5 pA/pF to 4.8+/-0.5 pA/pF (P<0.01) and I(Kur) from 3.6+/-0.5 pA/pF to 1.9+/-0.3 pA/pF (P<0.01) at +50 mV. I(to) was inhibited in a voltage-dependent manner, being significantly attenuated at test potentials from +10 to +50 mV, whereas the inhibition of I(Kur) was independent. The concentration giving a 50% inhibition was 0.50 microM for I(to) and 0.39 microM for I(Kur). Voltage-dependence of activation, inactivation and time-dependent recovery from inactivation of I(to) were not altered by carvedilol. However, time to peak and time-dependent inactivation of I(to) were significantly accelerated, indicating an open channel blocking action. The findings indicate that carvedilol significantly inhibits the major repolarization K(+) currents I(to) and I(Kur) in human atrial myocytes.
Deng
Chunyu
C
Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou 510080, PR China.
Yu
Xiyong
X
Kuang
Sujuan
S
Zhang
Wenchang
W
Zhou
Zhiling
Z
Zhang
Kai
K
Qian
Weimin
W
Shan
Zhixin
Z
Yang
Min
M
Wu
Shulin
S
Lin
Shuguang
S
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology*; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers; D011412:Propanolamines; D000077261:Carvedilol