Regulation of Gating and Rundown of HCN Hyperpolarization-activated Channels by Exogenous and Endogenous PIP2

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Structured PICO

Population

Recombinant HCN2 channels and native HCN channels in rabbit sinoatrial cells

Intervention

Exogenous and endogenous phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and its synthetic analogues

Comparator

Control conditions (e.g., patch excision without PIP2, phosphatidylinositol)

Outcome

Voltage dependence of activation and rundown of HCN currentssurrogate

PI(4,5)P2 regulates both native and recombinant HCN channels, reversing or delaying the hyperpolarizing shift in activation known as rundown.

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May influence HCN-mediated pacemaking in rabbit SA node; leaves open whether PI(4,5)P2 pathways are therapeutic targets in human arrhythmias.

Pian et al. (2006) studied this question.

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May influence HCN-mediated pacemaking in rabbit SA node; leaves open whether PI(4,5)P2 pathways are therapeutic targets in human arrhythmias.