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Articles in PresS, published online ahead of print August 15, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00389.2002
Submitted on May 6, 2002
Accepted on August 9, 2002
1 Research Center, Montreal Heart Insitute, Montreal, Quebec, Canada; Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
2 Research Center, Montreal Heart Insitute, Montreal, Quebec, Canada
3 Research Center, Montreal Heart Insitute, Montreal, Quebec, Canada; Medicine, University of Montreal, Montreal, Quebec, Canada
4 Research Center, Montreal Heart Insitute, Montreal, Quebec, Canada; Medicine, University of Montreal, Montreal, Quebec, Canada; Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
* To whom correspondence should be addressed. E-mail: nattel{at}icm.umontreal.ca.
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 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 atrium or ventricle and compatible with a different molecular basis.
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