Single-Channel Properties Support a Potential Contribution of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels and I _f to Cardiac Arrhythmias

Abstract

Background-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.

Hyperpolarization-Activated Cation Channels: From Genes to Function

“…This estimate is in good agreement with very recent data (210). However, single-channel conductances that are 10 -30 times higher have been reported for cloned HCN channels (267) as well as for native cardiac (267) and neuronal I h (350). At this point, it is unclear how this major discrepancy can be explained.…”

“…It will be necessary to rigorously prove that the recorded currents are indeed HCN channel currents. For example, one problem with single-channel recording reported by Michels and co-workers (267,268) is that the ensemble records of single-channel activity poorly match known kinetic properties of HCN channel current based on whole cell recordings. This issue needs to be clarified in the future.…”

Connexin 43 acts as a cytoprotective mediator of signal transduction by stimulating mitochondrial KATP channels in mouse cardiomyocytes

“…Single-channel analysis was done using custom software only from 1-channel patches, as previously reported (13,37,43,44). Linear leak and capacity currents were digitally subtracted using the average currents of nonactive sweeps.…”

Cardinal roles of miRNA in cardiac development and disease

“…These proteins are key components of the pacemaker channel involved in the hyperpolarization-activated current (I f ). They are also upregulated during cardiac hypertrophy and failure, and have been implicated in arrhythmogenesis [56]. The downregulation of miR-133 during cardiac hypertrophy is also associated with a decrease in K cnip2, the I to,f accessory subunit, albeit via an indirect mechanism, and is accordingly, responsible for prolongation of the QT interval [57].…”