Functional Role of the HCN4 Encoded 'Funny Current' in Human Sinus Node Pacemaker Cells

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Abstract

We recently reported patch clamp data on the voltage dependence of HCN4 channels expressed in human cardiomyocyte progenitor cells. Their half-activation voltage was 15 mV less negative than previously observed for the HCN4 encoded hyperpolarization-activated funny current' (I{f}) in isolated human sinus node cells. The time constant of (de)activation vs. voltage relationship showed a similar less negative voltage dependence as well as a 38% higher peak. We assessed the functional effects of these differences in I{f} kinetics in the Fabbri-Severi model of a single human sinus node pacemaker cell. The +15 mV shift in half-activation voltage per se resulted in a substantial increase in I{f}, carrying 85 vs. 59% of the net diastolic depolarizing charge, and a 14% shortening of the cycle length from 813 to 699 ms. This effect was counteracted by the time constant vs. voltage relationship, which caused a slower activation of I{f} in the diastolic membrane potential range. The resulting net effect was a 5.4% shortening of the cycle length from 813 to 770 ms, with I{f} carrying 59% of the net diastolic charge, and limited effects on the autonomic modulation of pacing rate by isoprenaline and acetylcholine. We conclude that the absolute value of the half-activation voltage of I{f} may be less indicative of the functional role of I{f} than commonly assumed.
Original languageEnglish
Title of host publication2021 Computing in Cardiology, CinC 2021
PublisherIEEE Computer Society
Volume2021-September
ISBN (Electronic)9781665479165
DOIs
Publication statusPublished - 2021
Event2021 Computing in Cardiology, CinC 2021 - Brno, Czech Republic
Duration: 13 Sept 202115 Sept 2021

Publication series

NameComputing in Cardiology

Conference

Conference2021 Computing in Cardiology, CinC 2021
Country/TerritoryCzech Republic
CityBrno
Period13/09/202115/09/2021

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