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September 27, 2002Journal of Biological ChemistryOpen Access

Interaction between Fast and Ultra-slow Inactivation in the Voltage-gated Sodium Channel

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Population

Xenopus oocytes expressing rat skeletal muscle Na(+) channel mu(1) with mutation A1529D (DIV-A1529D)

Comparison

Coexpression of rat brain beta subunit or… vs Channels without beta subunit or without…

Design

Preclinical

Authors

KHKarlheinz HilberWSWalter SandtnerOKOliver Kudlacek

Discussion

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Overview

Hypothesis-generating for sodium channel gating; leaves open relevance to human channelopathies or therapies.

Structured PICO

P
Population
Xenopus oocytes expressing rat skeletal muscle Na(+) channel mu(1) with mutation A1529D (DIV-A1529D)
I
Intervention
Coexpression of rat brain beta(1) subunit or introduction of mutations I1303Q/F1304Q/M1305Q to stabilize or destabilize the fast inactivated state
C
Comparator
Channels without beta(1) subunit or without destabilizing mutations
O
Outcome
Time course of entry to the ultra-slow inactivated state (USI) and occurrence of USIsurrogate

Fast inactivation inhibits ultra-slow inactivation in DIV-A1529D sodium channels, suggesting that binding to the inner pore of the fast inactivation gate stabilizes the channel structure.

Cite This Study

Hilber et al. (2002) studied this question.

synapsesocial.com/papers/6a707f4e3ce530166bc2d894https://doi.org/10.1074/jbc.m205661200
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1External pore residue mediates slow inactivation in mu 1 rat skeletal muscle sodium channels.1996 · 136 citations
  2. 2Coupling between fast and slow inactivation revealed by analysis of a point mutation (F1304Q) in mu 1 rat skeletal muscle sodium channels.1996 · 35 citations
  3. 3A Critical Role for Transmembrane Segment IVS6 of the Sodium Channel α Subunit in Fast Inactivation1995 · 174 citations
  4. 4Movement of Voltage Sensor S4 in Domain 4 Is Tightly Coupled to Sodium Channel Fast Inactivation and Gating Charge Immobilization1999 · 86 citations
  5. 5The adult rat brain beta 1 subunit modifies activation and inactivation gating of multiple sodium channel alpha subunits1994 · 200 citations