Abstract
The slow delayed rectifier K+ current (IKs) is present in sinoatrial node (SAN) cells of various species, but data on the contribution of IKs to SAN pacemaker activity are not consistent. Yet, sinus bradycardia is a common finding in case of gain-of-function mutations in the KCNQ1 gene, encoding the pore-forming α-subunit of the IKs channel.
We carried out computer simulations of human SAN pacemaker activity using the Fabbri–Severi model of a single human SAN cell. Biophysical properties of IKs were updated, based on our recent patch clamp data on IKs channels expressed in HEK-293 cells.
Under vagal tone, block of the original IKs of the Fabbri–Severi model had only a marginally small effect on action potential duration and diastolic depolarization, and thus cycle length. However, with the formulation of IKs based on our patch clamp data, block of IKs had a substantial effect on diastolic depolarization and cycle length, increasing pacing rate by 17%. A qualitatively similar, but less substantial effect was observed under control conditions and under β-adrenergic tone, with an increase in pacing rate of 5.2% in either case. Simulation of a gain-of-function mutation in KCNQ1 revealed a strong bradycardic effect during vagal tone.
We conclude that IKs contributes to human SAN pacemaker activity at all levels of autonomic tone.
We carried out computer simulations of human SAN pacemaker activity using the Fabbri–Severi model of a single human SAN cell. Biophysical properties of IKs were updated, based on our recent patch clamp data on IKs channels expressed in HEK-293 cells.
Under vagal tone, block of the original IKs of the Fabbri–Severi model had only a marginally small effect on action potential duration and diastolic depolarization, and thus cycle length. However, with the formulation of IKs based on our patch clamp data, block of IKs had a substantial effect on diastolic depolarization and cycle length, increasing pacing rate by 17%. A qualitatively similar, but less substantial effect was observed under control conditions and under β-adrenergic tone, with an increase in pacing rate of 5.2% in either case. Simulation of a gain-of-function mutation in KCNQ1 revealed a strong bradycardic effect during vagal tone.
We conclude that IKs contributes to human SAN pacemaker activity at all levels of autonomic tone.
Original language | English |
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Title of host publication | 2022 Computing in Cardiology, CinC 2022 |
Subtitle of host publication | Proceedings of the 2022 Computing in Cardiology conference |
Publisher | IEEE Computer Society |
Number of pages | 4 |
Publication status | Accepted/In press - 2022 |
Event | Computing in Cardiology 2022: 49th Computing in Cardiology Conference - Tampere Hall, Tampere, Finland Duration: 4 Sept 2022 → 7 Sept 2022 https://events.tuni.fi/cinc2022/ |
Publication series
Name | Computing in Cardiology |
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Publisher | IEEE Computer Society |
Conference
Conference | Computing in Cardiology 2022 |
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Abbreviated title | CinC 2022 |
Country/Territory | Finland |
City | Tampere |
Period | 4/09/2022 → 7/09/2022 |
Internet address |