Extracellular salt bridge networks around S4 implicated in HCN channel gating and heart disease

Proceedings of the National Academy of Sciences, Volume 122, Issue 37, September 2025. <br/>SignificanceHyperpolarization-activated cyclic nucleotide-gated (HCN) channels have an extracellularly extended S4 segment. However, whether this long S4 contributes to gating is still unknown. Here, we elucidated the functional contribution of the …