Table 3.

Regulatory mechanisms altering I_h/I_f activation kinetics

Modulatory mechanism or treatment	Experimental system	Increased or decreased rate of activation	Ref.
cAMP	Numerous	Increased	1–8
PIP2	Oocytes expressing HCN2 (inside-out patch)	Decreased at some but not all tested potentials	41, 46, 47
[pH]i	Rat TC neurons or HEK293 cells expressing HCN2	Increased with ↑pH; decreased with ↓pH	49, 50, 54
[pH]o	FLP-IN-293 cells expressing HCN1 or HCN4	Increased with ↓pH	51
Genistein (tyrosine kinase inhibition)	Oocytes expressing HCN1, 2 or 4	Decreased for HCN2 and 4, no effect for HCN1	57
	Rat ventricular myocytes	Decreased
Src kinase	HEK293 cells expressing HCN2 treated with PP2 (Src inhibitor)	Decreased with PP2 treatment	60
Proteolysis of HCN channel subunits	Coexpression of proteolyzed HCN2 (HCN2ΔC) with HCN4 in HEK293 cells	Increased compared to HCN4 alone	66
KCNE2	Oocytes expressing HCN1 and HCN2	Increased	85
	Oocytes or CHO cells expressing HCN4	Decreased	90
	Adenoviral overexpression in cultured neonatal rat ventricular myocytes	Increased	89
	CHO cells expressing HCN1, 2, 4	Increased	88
TRIP8b	Oocytes expressing HCN1	Decreased	107
Filamin A	Coexpression with HCN1 in melanoma cell line	Decreased	94

Magnitude is not included here as it is typically dependent upon voltage step.