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HCN4 activates 3',5'-cyclic AMP. 4 / 4
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"The first one was the p.R524Q HCN4 variant, that increases the channel affinity for cAMP and was described in an Italian family with symptomatic sinus tachyarrhythmia (17)."
38032931
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"[7, 13–15]Two I antagonist drugs (ivabradine [16] and ZD7288 [17]) prevented SAN thermal rate responses (Q = 1.27±0.08 for ivabradine and 1.18±0.04 for ZD7822, p<0.001 as compared to control condition, Fig 1c and d), without affecting rate increases from isoproterenol (Fig S1a), a β-adrenergic receptor agonist that accelerates heart rate by HCN4 and cAMP dependent and independent pathways."
37693513
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"In heterologous cells, the C-terminal-truncated HCN2 protein co-assembles with HCN4 to form functional heteromeric HCN channels, which activate faster than homomeric HCN2 or homomeric HCN4 channels, and display properties similar to endogenous myocardial I (f) channels Taken together, these results suggest that functional myocardial I (f) channels reflect the heteromeric assembly of HCN2 and HCN4 subunits and further that the HCN4 subunit underlies the cAMP mediated regulation of cardiac I (f) channels."
19574228
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"This conclusion is supported by data showing that deletion of αDE in HCN4 drastically reduces the cAMP affinity by about 30-fold in patch experiments."
38287019