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1 Research Center, Montreal Heart Institute, Montreal, Quebec H1T 1C8; 2 Department of Medicine, University of Montreal, Montreal, Quebec H3C 3J7; and 3 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada
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°C with
whole cell patch clamp. PCs had clear inward rectifier K+
current (IK1), 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
(Ito) density was smaller, but end pulse
sustained current (Isus) was larger, in PCs vs.
VMs. Ito recovery was substantially slower in
PCs, leading to strong frequency dependence. Unlike VM
Ito, which was unaffected by 10 mM
tetraethylammonium, Purkinje Ito was strongly
inhibited by tetraethylammonium, and Purkinje
Ito was 10-fold more sensitive to
4-aminopyridine than VM. PC Isus was also
reduced strongly by 10 mM tetraethylammonium. In conclusion, human PCs
demonstrate a prominent IK1, a time-dependent
hyperpolarization-activated current, and an Ito
with pharmacological sensitivity and recovery kinetics different from
those in the atrium or ventricle and compatible with a different
molecular basis.
ion currents; cardiac Purkinje cells; potassium channel blockers
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