Show simple item record

dc.contributor.authorRothberg, Brad S.
dc.contributor.authorShin, Ki Soon
dc.contributor.authorYellen, Gary
dc.date.accessioned2019-10-05T16:06:03Z
dc.date.issued2003
dc.identifier.citationRothberg, Brad S., Ki Soon Shin, and Gary Yellen. 2003. “Movements near the Gate of a Hyperpolarization-Activated Cation Channel.” The Journal of General Physiology 122 (5): 501–10. https://doi.org/10.1085/jgp.200308928.
dc.identifier.issn0022-1295
dc.identifier.issn1540-7748
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483561*
dc.description.abstractHyperpolarization-activated cation (HCN) channels regulate pacemaking activity in cardiac cells and neurons. Like the related depolarization-activated K+ channels (Kv channels), HCN channels use an intracellular activation gate to regulate access to an inner cavity, lined by the S6 transmembrane regions, which leads to the selectivity filter near the extracellular surface. Here we describe two types of metal interactions with substituted cysteines in the S6, which alter the voltage-controlled movements of the gate. At one position (1,466), substitution of cysteine in all four subunits allows Cd2+ ions at nanomolar concentration to stabilize the open state (a "lock-open" effect). This effect depends on native histidines at a nearby position (H462); the lock-open effect can be abolished by changing the histidines to tyrosines, or enhanced by changing them to cysteines. Unlike a similar effect in Kv channels, this effect depends on a Cd2+ bridge between 462 and 466 in the same subunit. Cysteine substitution at another position (Q468) produces two effects of Cd2+: both a lock-open effect and a dramatic slowing of channel activation-a "lock-closed" effect. The two effects can be separated, because the lock-open effect depends oil the histidine at position 462. The novel lock-closed effect, results from stabilization of the closed state by the binding of tip to four Cd2+ ions. During the opening conformational change, the S6 apparently moves from one position in which the 468C cysteines can bind four Cd2+ ions, possibly as a cluster of cysteines and cadmium ions near the central axis of the pore, to another position (or flexible range of positions) where either 466C or 468C can bind Cd2+ in association with the histidine at 462.
dc.language.isoen_US
dc.publisherRockefeller University Press
dash.licenseLAA
dc.titleMovements near the Gate of a Hyperpolarization-activated Cation Channel
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalThe Journal of General Physiology
dash.depositing.authorYellen, Gary::1d0fa5f147cd32c6d6da09c3aef17e5b::600
dc.date.available2019-10-05T16:06:03Z
dash.workflow.comments1Science Serial ID 110809
dc.identifier.doi10.1085/jgp.200308928
dash.source.volume122;5


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record