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• W2022374494 abstract "The pacemaker current I(f) is present in atrial and ventricular myocytes. However, it remains controversial whether I(f) overexpression in diseased states might play a role for arrhythmogenesis, because first I(f) activation in whole-cell recordings hardly overlapped the diastolic voltage of working myocardium.To obtain further insight into I(HCN) and I(f) properties, we provide for the first time detailed single-channel analysis of heterologously expressed hyperpolarization-activated cyclic nucleotide-gated (HCN) isoforms and native human I(f). HCN subtypes differed significantly in single-channel amplitude, conductance, and activation kinetics. Interestingly, threshold potentials of HCN isoforms were more positive than would have been expected from whole-cell measurements. Single-channel properties of cells cotransfected with HCN2 and HCN4 were distinct from cells expressing HCN2 or HCN4 alone, demonstrating that different HCN isoforms can influence current properties of a single HCN channel complex, thus providing direct functional evidence for HCN heteromerization. Pooled data of homomeric and heteromeric HCN channels and of native I(f) extrapolated from maximum likelihood fits indicated a multistate gating scheme comprising 5 closed- and 4 open-channel states. Single-channel characteristics of I(f) in human atrial myocytes closely resembled those of HCN4 or HCN2+HCN4, supporting the hypothesis that native I(f) channels in atrial myocardium are heteromeric complexes composed of HCN4 and/or HCN2. Most interestingly, half-maximal activation of single-channel atrial I(f) (-68.3+/-4.9 mV; k=-9.9+/-1.5; n=8) was well within the diastolic voltage range of human atrial myocardium.These observations support a potential contribution of HCN/I(f) to the arrhythmogenesis of working myocardium under pathological conditions." @default.
• W2022374494 created "2016-06-24" @default.
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• W2022374494 date "2005-02-01" @default.
• W2022374494 modified "2023-09-27" @default.
• W2022374494 title "Single-Channel Properties Support a Potential Contribution of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels and <i>I</i> _f to Cardiac Arrhythmias" @default.
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• W2022374494 doi "https://doi.org/10.1161/01.cir.0000153799.65783.3a" @default.
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