Properties of potassium currents in Purkinje cells of failing human hearts.
Cardiac Purkinje fibers play an important role in cardiac arrhythmias, but no information is available about ionic currents in human cardiac Purkinje cells (PCs). PCs and midmyocardial ventricular myocytes (VMs) were isolated from explanted human hearts. K(+) currents were evaluated at 37 degrees C with whole cell patch clamp. PCs had clear inward rectifier K(+) current (I(K1)), with a density not significantly different from VMs between -110 and -20 mV. A Cs(+)-sensitive, time-dependent hyperpolarization-activated current was measurable negative to -60 mV. Transient outward current (I(to)) density was smaller, but end pulse sustained current (I(sus)) was larger, in PCs vs. VMs. I(to) recovery was substantially slower in PCs, leading to strong frequency dependence. Unlike VM I(to), which was unaffected by 10 mM tetraethylammonium, Purkinje I(to) was strongly inhibited by tetraethylammonium, and Purkinje I(to) was 10-fold more sensitive to 4-aminopyridine than VM. PC I(sus) was also reduced strongly by 10 mM tetraethylammonium. In conclusion, human PCs demonstrate a prominent I(K1), a time-dependent hyperpolarization-activated current, and an I(to) with pharmacological sensitivity and recovery kinetics different from those in the atrium or ventricle and compatible with a different molecular basis.
Han
Wei
W
Research Center, Montreal Heart Institute, Quebec H1T 1C8, Canada.
Zhang
Liming
L
Schram
Gernot
G
Nattel
Stanley
S
D000328:Adult; D002469:Cell Separation; D054815:Cyclic Nucleotide-Gated Cation Channels; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000378:metabolism; D011690:Purkinje Fibers / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011188:Potassium