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dc.contributor.authorProenza, Catherine
dc.contributor.authorYellen, Gary
dc.date.accessioned2019-10-05T16:05:53Z
dc.date.issued2006
dc.identifier.citationProenza, Catherine, and Gary Yellen. 2006. “Distinct Populations of HCN Pacemaker Channels Produce Voltage-Dependent and Voltage-Independent Currents.” The Journal of General Physiology 127 (2): 183–90. https://doi.org/10.1085/jgp.200509389.
dc.identifier.issn0022-1295
dc.identifier.issn1540-7748
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483548*
dc.description.abstractHyperpolarization-activated HCN pacemaker channels are critical for the generation of spontaneous activity and the regulation of excitability in the heart and in many types of neurons. These channels produce both a voltage-dependent current (I-h) and a voltage-independent current (I-inst or VIC). In this study, we explored the molecular basis of the voltage-independent current. We found that for the spHCN isoform, VIC averaged similar to 4% of the maximum HCN conductance that could be activated by hyperpolarization. Cyclic AMP increased the voltage-independent current in spHCN to similar to 8% of maximum. In HCN2, VIC was similar to 2% of the maximal current, and was little affected by cAMP. VIC in both spHCN and HCN2 was blocked rapidly both by ZD7288 (an HCN channel blocker that is thought to bind in the conduction pore) and by application of Cd2+ to channels containing an introduced cysteine in the pore (spHCN-464C or HCN2-436C). These results suggest that VIC flows through the main conduction pathway, down the central axis of the protein. We suspected that VIC simply represented a nonzero limiting open probability for HCN channels at positive voltages. Surprisingly, we found instead that the spHCN channels carrying VIC were not in rapid equilibrium with the channels carrying the voltage-dependent current, because they could be blocked independently; a single application of blocker at a depolarized potential essentially eliminated VIC with little change in Ih. Thus, VIC appears to be produced by a distinct population of HCN channels. This voltage-independent current could contribute significantly to the role of HCN channels in neurons and myocytes; VIC flowing through the channels at physiological potentials would tend to promote excitability by accelerating both depolarization and repolarization.
dc.language.isoen_US
dc.publisherRockefeller University Press
dash.licenseLAA
dc.titleDistinct Populations of HCN Pacemaker Channels Produce Voltage-dependent and Voltage-independent Currents
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalThe Journal of General Physiology
dash.depositing.authorYellen, Gary::1d0fa5f147cd32c6d6da09c3aef17e5b::600
dc.date.available2019-10-05T16:05:53Z
dash.workflow.comments1Science Serial ID 110811
dc.identifier.doi10.1085/jgp.200509389
dash.source.volume127;2
dash.source.page183


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