ArticleBiophysical journal2011
Molecular determinants of U-type inactivation in Kv2.1 channels.
Article in Biophysical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Molecular mechanism responsible for sex differences in electrical activity of mouse pancreatic β cells.JCI insight · 2024Article
- A novel autism-associatedFrontiers in cellular neuroscience · 2024Article
- Mechanism of use-dependent Kv2 channel inhibition by RY785.The Journal of general physiology · 2022Article
- KV1.2 channels inactivate through a mechanism similar to C-type inactivation.The Journal of general physiology · 2020Article
- The Selectivity Filter Is Involved in the U-Type Inactivation Process of Kv2.1 and Kv3.1 Channels.Biophysical journal · 2020Article
- Gating and Regulation of KCNQ1 and KCNQ1 + KCNE1 Channel Complexes.Frontiers in physiology · 2020Review
- De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing.Scientific reports · 2015Article
- Modulation of Closed-State Inactivation in Kv2.1/Kv6.4 Heterotetramers as Mechanism for 4-AP Induced Potentiation.PloS one · 2015Article
- The Inhibitory Effects of Ca2+ Channel Blocker Nifedipine on Rat Kv2.1 Potassium Channels.PloS one · 2015Article
- Shaker IR T449 mutants separate C- from U-type inactivation.The Journal of membrane biology · 2014Article
- Role of outer-pore residue Y380 in U-type inactivation of KV2.1 channels.The Journal of membrane biology · 2013Article
- Shab K (+) channel slow inactivation: a test for U-type inactivation and a hypothesis regarding K (+) -facilitated inactivation mechanisms.Channels (Austin, Tex.)Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kv2.1 channels exhibit a U-shaped voltage-dependence of inactivation that is thought to represent preferential inactivation from preopen closed states. However, the molecular mechanisms underlying so-called U-type inactivation are unknown. We have performed a cysteine scan of the S3-S4 and S5-P-loop linkers and found sites that are important for U-type inactivation. In the S5-P-loop linker, U-type inactivation was preserved in all mutant channels except E352C. This mutation, but not E352Q, abolished closed-state inactivation while preserving open-state inactivation, resulting in a loss of the U-shaped voltage profile. The reducing agent DTT, as well as the C232V mutation in S2, restored U-type inactivation to the E352C mutant, which suggests that residues 352C and C232 may interact to prevent U-type inactivation. The R289C mutation, in the S3-S4 linker, also reduced U-type inactivation. In this case, DTT had little effect but application of MTSET restored wild-type-like U-type inactivation behavior, suggestive of the importance of charge at this site. Kinetic modeling suggests that the E352C and R289C inactivation phenotypes largely resulted from reductions in the rate constants for transitions from closed to inactivated states. The data indicate that specific residues within the S3-S4 and S5-P-loop linkers may play important roles in Kv2.1 U-type inactivation.
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