Reversal of HCN channel voltage dependence via bridging of the S4-S5 linker and Post-S6.

ABSTRACT: Voltage-gated ion channels possess charged domains that move in response to changes in transmembrane voltage. How this movement is transduced into gating of the channel pore is largely unknown. Here we show directly that two functionally important regions of the spHCN1 pacemaker channel, the S4-S5 linker and the C-linker, come into close proximity during gating. Cross-linking these regions with high-affinity metal bridges or disulfide bridges dramatically alters channel gating in the absence of cAMP; after modification the polarity of voltage dependence is reversed. Instead of being closed at positive voltage and activating with hyperpolarization, modified channels are closed at negative voltage and activate with depolarization. Mechanistically, this reversal of voltage dependence occurs a

SUBMITTER: Prole DL 

PROVIDER: S-EPMC2151568 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature