KCNIP1

Last update 23 Jan 2025

Basic Info

Synonyms

A-type potassium channel modulatory protein 1, KCHIP1, KCNIP1

+ [5]

Introduction

Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Regulates channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. In vitro, modulates KCND1/Kv4.1 and KCND2/Kv4.2 currents. Increases the presence of KCND2 at the cell surface.

100 Clinical Results associated with KCNIP1

100 Translational Medicine associated with KCNIP1

0 Patents (Medical) associated with KCNIP1

133

Literatures (Medical) associated with KCNIP1

01 Jun 2024·Neurobiology of Disease

The downregulation of Kv1 channels in Lgi1 mice is accompanied by a profound modification of its interactome and a parallel decrease in Kv2 channels

Article

Author: Ramirez-Franco, Jorge ; Sangiardi, Marion ; Lee, Suk-Ho ; Debreux, Kévin ; Seagar, Michael ; Lévêque, Christian ; Kim, Yujin ; Belghazi, Maya ; El Far, Oussama

In animal models of LGI1-dependent autosomal dominant lateral temporal lobe epilepsy, Kv₁ channels are downregulated, suggesting their crucial involvement in epileptogenesis. The molecular basis of Kv₁ channel-downregulation in LGI1 knock-out mice has not been elucidated and how the absence of this extracellular protein induces an important modification in the expression of Kv₁ remains unknown. In this study we analyse by immunofluorescence the modifications in neuronal Kv_1.1 and Kv_1.2 distribution throughout the hippocampal formation of LGI1 knock-out mice. We show that Kv₁ downregulation is not restricted to the axonal compartment, but also takes place in the somatodendritic region and is accompanied by a drastic decrease in Kv₂ expression levels. Moreover, we find that the downregulation of these Kv channels is associated with a marked increase in bursting patterns. Finally, mass spectrometry uncovered key modifications in the Kv₁ interactome that highlight the epileptogenic implication of Kv₁ downregulation in LGI1 knock-out animals.

01 May 2024·Journal of Clinical Investigation

Induction of antiviral interferon-stimulated genes by neuronal STING promotes the resolution of pain in mice

Article

Author: Soubeyre, Vanessa ; Agosti, Francina ; Lonjon, Nicolas ; Vachiery-Lahaye, Florence ; Gill, Gurveer ; Bauchet, Luc ; Chiu, Isaac M ; Bourinet, Emmanuel ; Basso, Lilian ; Bradaia, Amyaouch ; Iftinca, Mircea ; Defaye, Manon ; Svendsen, Kristofer ; Poulen, Gaetan ; Ozmaeian, Aye ; Gheziel, Nadine ; Abdullah, Nasser S ; Martin, Jérémy ; Altier, Christophe ; Delanne-Cuménal, Mélissa

Inflammation and pain are intertwined responses to injury, infection, or chronic diseases. While acute inflammation is essential in determining pain resolution and opioid analgesia, maladaptive processes occurring during resolution can lead to the transition to chronic pain. Here we found that inflammation activates the cytosolic DNA-sensing protein stimulator of IFN genes (STING) in dorsal root ganglion nociceptors. Neuronal activation of STING promotes signaling through TANK-binding kinase 1 (TBK1) and triggers an IFN-β response that mediates pain resolution. Notably, we found that mice expressing a nociceptor-specific gain-of-function mutation in STING exhibited an IFN gene signature that reduced nociceptor excitability and inflammatory hyperalgesia through a KChIP1-Kv4.3 regulation. Our findings reveal a role of IFN-regulated genes and KChIP1 downstream of STING in the resolution of inflammatory pain.

17 Feb 2024·Clinical Infectious Diseases

Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia

Article

Author: Doernberg, Sarah ; Howard-Anderson, Jessica ; Hamasaki, Toshimitsu ; Holland, Thomas L. ; Nambiar, Sumati ; Hamasaki, Toshi ; Evans, Scott R. ; Doernberg, Sarah B. ; Collyar, Deborah ; Kinamon, Tori ; Holland, Tom ; Chambers, Henry F. ; Hill, Carol ; Tsalik, Ephraim ; Fowler, Vance ; Leister-Tebbe, Heidi ; Boucher, Helen W. ; Evans, Scott ; Geres, Holly ; Rubin, Daniel ; Rubin, Dan ; Dai, Weixiao ; King, Heather ; Kim, Peter ; Natarajan, Mukil ; Boucher, Helen ; Fowler, Vance G. Jr. ; Nambiar, Sumathi ; Needles, Mark ; Cosgrove, Sara ; Waack, Ursula ; Gopinath, Danaher Ramya

AbstractBackgroundHospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk evaluation.MethodsA multidisciplinary committee created an infectious diseases DOOR endpoint customized for HABP/VABP, incorporating infectious complications, serious adverse events, and mortality. We applied this to 2 previously completed, large randomized controlled trials for HABP/VABP. ZEPHyR compared vancomycin to linezolid and VITAL compared linezolid to tedizolid. For each trial, we evaluated the DOOR distribution and probability, including DOOR component and partial credit analyses. We also applied DOOR in subgroup analyses.ResultsIn both trials, the HABP/VABP DOOR demonstrated similar overall clinical outcomes between treatment groups. In ZEPHyR, the probability that a participant treated with linezolid would have a more desirable outcome than a participant treated with vancomycin was 50.2% (95% confidence interval [CI], 45.1%−55.3%). In VITAL, the probability that a participant treated with tedizolid would have a more desirable outcome than a participant treated with linezolid was 48.7% (95% CI, 44.8%–52.6%). The DOOR component analysis revealed that participants treated with tedizolid had a less desirable outcome than those treated with linezolid when considering clinical response alone. However, participants with decreased renal function had improved overall outcomes with tedizolid.ConclusionsThe HABP/VABP DOOR provided more granular information about clinical outcomes than is typically presented in clinical trials. HABP/VABP trials would benefit from prospectively using DOOR.

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KCNIP1

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