ArticleChannels (Austin, Tex.)2009
A novel N-terminal motif of dipeptidyl peptidase-like proteins produces rapid inactivation of KV4.2 channels by a pore-blocking mechanism.
Article in Channels (Austin, Tex.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Beyond the Alpha Subunit: Pharmacological Modulation of Kv4.2 Channels by Ancillary Proteins.Cells · 2026Review
- Neuronal Roles of the Multifunctional Protein Dipeptidyl Peptidase-like 6 (DPP6).International journal of molecular sciences · 2022Review
- Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets.Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- KFrontiers in cellular neuroscience · 2020Review
- Article
- A-Type KFrontiers in molecular neuroscience · 2018Review
- Kv4.2 and accessory dipeptidyl peptidase-like protein 10 (DPP10) subunit preferentially form a 4:2 (Kv4.2:DPP10) channel complex.The Journal of biological chemistry · 2015Article
- Structure of human dipeptidyl peptidase 10 (DPPY): a modulator of neuronal Kv4 channels.Scientific reports · 2015Article
- Update on the implication of potassium channels in autism: K(+) channelautism spectrum disorder.Frontiers in cellular neuroscience · 2015Review
- Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation.Human molecular genetics · 2014Article
- Modulatory mechanisms and multiple functions of somatodendritic A-type K (+) channel auxiliary subunits.Frontiers in cellular neuroscience · 2014Review
- S-glutathionylation of an auxiliary subunit confers redox sensitivity to Kv4 channel inactivation.PloS one · 2014Article
- A new TASK for Dipeptidyl Peptidase-like Protein 6.PloS one · 2013Article
- Modeling-independent elucidation of inactivation pathways in recombinant and native A-type Kv channels.The Journal of general physiology · 2012Article
- Article
- Voltage sensor inactivation in potassium channels.Frontiers in pharmacology · 2012Article
- Mechanisms of closed-state inactivation in voltage-gated ion channels.The Journal of physiology · 2011Review
- Dipeptidyl peptidase-like protein 6 is required for normal electrophysiological properties of cerebellar granule cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Impaired glycosylation blocks DPP10 cell surface expression and alters the electrophysiology of Ito channel complex.Pflugers Archiv : European journal of physiology · 2010Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The somatodendritic subthreshold A-type K(+) current in neurons (I(SA)) depends on its kinetic and voltage-dependent properties to regulate membrane excitability, action potential repetitive firing, and signal integration. Key functional properties of the K(V)4 channel complex underlying I(SA) are determined by dipeptidyl peptidase-like proteins known as dipeptidyl peptidase 6 (DPP6) and dipeptidyl peptidase 10 (DPP10). Among the multiple known DPP10 isoforms with alternative N-terminal sequences, DPP10a confers exceptionally fast inactivation to K(V)4.2 channels. To elucidate the molecular basis of this fast inactivation, we investigated the structure-function relationship of the DPP10a N-terminal region and its interaction with the K(V)4.2 channel. Here, we show that DPP10a shares a conserved N-terminal sequence (MNQTA) with DPP6a (aka DPP6-E), which also induces fast inactivation. Deletion of the NQTA sequence in DPP10a eliminates this dramatic fast inactivation, and perfusion of MNQTA peptide to the cytoplasmic face of inside-out patches inhibits the K(V)4.2 current. DPP10a-induced fast inactivation exhibits competitive interactions with internally applied tetraethylammonium (TEA), and elevating the external K(+) concentration accelerates recovery from DPP10a-mediated fast inactivation. These results suggest that fast inactivation induced by DPP10a or DPP6a is mediated by a common N-terminal inactivation motif via a pore-blocking mechanism. This mechanism may offer an attractive target for novel pharmacological interventions directed at impairing I(SA) inactivation and reducing neuronal excitability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.