Gating mechanisms in hyperpolarization-activated cyclic nucleotide-gated ion channels

摘要: Hyperpolarization-activated cyclic nucleotide-gated 1on channels (HCN) are gated by voltage, that is, they able to detect changes in voltage and convert into work for opening closing (gating) the channel gate. The focus of this thesis was investigate gating mechanisms HCN channels. Results from these experiments revealed have a sensor (S4) similar K v but reversed gating. This makes up first half thesis. In addition, outward currents through susceptible voltage-dependent block intracellular Mg +. relating Mg+ make second mediate an inward cation current contributes spontaneous rhythmic firing activity heart brain. These share homology with depolarization-activated Kv channels, including six transmembrane domains (S 1-S6) positively charged S4 segment. domain has been shown function as undergo movement Shaker K+ channel. Experiments making thesis, incorporated substituted cysteine accessibility method conjunction two-electrode clamp test state dependent HCNl. Six mutations (R247C, T249C, 1251C, S253C, L254C, S261 C) were used assess heterologously expressed HCNl Xenopus oocytes. State-dependent found four residues, T249C S253C extracellular solution