What question did this study set out to answer?

This study aims to examine the blocking action of ivabradine on HCN1 and HCN4 channels in cardiac tissue.

February 17, 2006The Journal of PhysiologyOpen Access

Properties of ivabradine‐induced block of HCN1 and HCN4 pacemaker channels

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Population

Mouse (m) HCN1 and human (h) HCN4 channels heterologously expressed in HEK 293 cells

Design

Preclinical

Authors

ABAnnalisa BucchiUniversity of Milan ATA. TognatiUniversity of Milan RMRaffaella MilanesiUniversity of Milan

Discussion

Member takes

Implication

Does not support changes in ivabradine use; leaves open clinical impact of isoform-specific HCN block.

Key Points

This study aims to examine the blocking action of ivabradine on HCN1 and HCN4 channels in cardiac tissue.
Investigated ivabradine's effects on mouse HCN1 and human HCN4 channels expressed in HEK 293 cells.
Measured the dose-dependent blocking action and half-block concentrations of both channels.
Analyzed the impact of current flow direction and channel states (open vs. closed) on the blocking mechanism.
Ivabradine blocked hHCN4 with a half-block concentration of 2.0 microm and showed increased effectiveness with channel depolarization.
Block of mHCN1 was observed at 0.94 microm, requiring closed or transitional states, not relieved during hyperpolarization.
Indicates ivabradine acts as an 'open-channel' blocker for hHCN4 and a 'closed-channel' blocker for mHCN1.

Structured PICO

Population

Mouse (m) HCN1 and human (h) HCN4 channels heterologously expressed in HEK 293 cells

Intervention

Ivabradine

Outcome

Blocking action and properties of ivabradine on HCN channels (dose-dependence, half-block concentrations, state-dependence)surrogate

Ivabradine exhibits distinct state-dependent blocking mechanisms on different pacemaker channel isoforms, acting as an open-channel blocker for human HCN4 and a closed-channel blocker for mouse HCN1.

Cite This Study

Bucchi et al. (2006) studied this question.

synapsesocial.com/papers/6a6fa28df44fa9f079dd1a06 https://doi.org/10.1113/jphysiol.2005.100776

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Properties of ivabradine‐induced block of HCN1 and HCN4 pacemaker channels

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Properties of ivabradine‐induced block of HCN1 and HCN4 pacemaker channels

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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