抄録
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels contribute to rhythmic activity, membrane excitability, and synaptic transmission. We previously isolated cDNA for HCN4. HCN1 showed the fastest activation kinetics while HCN4 showed the slowest. We previously reported that the different kinetics among subtypes are generated mainly by S1 and the S1-S2 loop in HCN channels. Here, we investigated the structural basis of the ability of S1 to affect the voltage-dependency by introducing mutations in S1. We found that one Tryptophan mutation introduced in the middle of S1 (L139W) induced a positive voltage-shift of activation by 87 mV with an incomplete closure even at an extremely depolarizing potential. Further mutations at position 139 also disrupted channel closure and shifted the voltage-dependency. These results suggest that position 139 in S1 likely faces a mobile part of the S4 voltage sensor and may interact with it. [J Physiol Sci. 2007;57 Suppl:S223]
