scholarly journals Tyrosine Phosphatases ε and α Perform Specific and Overlapping Functions in Regulation of Voltage-gated Potassium Channels in Schwann Cells

2006 ◽  
Vol 17 (10) ◽  
pp. 4330-4342 ◽  
Author(s):  
Zohar Tiran ◽  
Asher Peretz ◽  
Tal Sines ◽  
Vera Shinder ◽  
Jan Sap ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cells ◽  
Tyrosine Phosphatases ◽  
Open Probability ◽  
Voltage Gated ◽  
Kv Channel ◽  
Kv Channels ◽  
Or Organization ◽  
Unexpected Difference

Tyrosine phosphatases (PTPs) ε and α are closely related and share several molecular functions, such as regulation of Src family kinases and voltage-gated potassium (Kv) channels. Functional interrelationships between PTPε and PTPα and the mechanisms by which they regulate K+ channels and Src were analyzed in vivo in mice lacking either or both PTPs. Lack of either PTP increases Kv channel activity and phosphorylation in Schwann cells, indicating these PTPs inhibit Kv current amplitude in vivo. Open probability and unitary conductance of Kv channels are unchanged, suggesting an effect on channel number or organization. PTPα inhibits Kv channels more strongly than PTPε; this correlates with constitutive association of PTPα with Kv2.1, driven by membranal localization of PTPα. PTPα, but not PTPε, activates Src in sciatic nerve extracts, suggesting Src deregulation is not responsible exclusively for the observed phenotypes and highlighting an unexpected difference between both PTPs. Developmentally, sciatic nerve myelination is reduced transiently in mice lacking either PTP and more so in mice lacking both PTPs, suggesting both PTPs support myelination but are not fully redundant. We conclude that PTPε and PTPα differ significantly in their regulation of Kv channels and Src in the system examined and that similarity between PTPs does not necessarily result in full functional redundancy in vivo.

scholarly journals Molecular Template for a Voltage Sensor in a Novel K+ Channel. I. Identification and Functional Characterization of KvLm, a Voltage-gated K+ Channel from Listeria monocytogenes

2006 ◽  
Vol 128 (3) ◽  
pp. 283-292 ◽  
Author(s):  
Jose S. Santos ◽  
Alicia Lundby ◽  
Cecilia Zazueta ◽  
Mauricio Montal
Keyword(s):  
Listeria Monocytogenes ◽  
Voltage Sensor ◽  
K Channel ◽  
Open Probability ◽  
Voltage Gated ◽  
Kv Channel ◽  
Kv Channels ◽  
Sensor Module ◽  
Single Channel Currents ◽  
Hallmark Feature

The fundamental principles underlying voltage sensing, a hallmark feature of electrically excitable cells, are still enigmatic and the subject of intense scrutiny and controversy. Here we show that a novel prokaryotic voltage-gated K+ (Kv) channel from Listeria monocytogenes (KvLm) embodies a rudimentary, yet robust, sensor sufficient to endow it with voltage-dependent features comparable to those of eukaryotic Kv channels. The most conspicuous feature of the KvLm sequence is the nature of the sensor components: the motif is recognizable; it appears, however, to contain only three out of eight charged residues known to be conserved in eukaryotic Kv channels and accepted to be deterministic for folding and sensing. Despite the atypical sensor sequence, flux assays of KvLm reconstituted in liposomes disclosed a channel pore that is highly selective for K+ and is blocked by conventional Kv channel blockers. Single-channel currents recorded in symmetric K+ solutions from patches of enlarged Escherichia coli (spheroplasts) expressing KvLm showed that channel open probability sharply increases with depolarization, a hallmark feature of Kv channels. The identification of a voltage sensor module in KvLm with a voltage dependence comparable to that of other eukaryotic Kv channels yet encoded by a sequence that departs significantly from the consensus sequence of a eukaryotic voltage sensor establishes a molecular blueprint of a minimal sequence for a voltage sensor.

DPP10 is an inactivation modulatory protein of Kv4.3 and Kv1.4

2006 ◽  
Vol 291 (5) ◽  
pp. C966-C976 ◽  
Author(s):  
Hong-Ling Li ◽  
Yu-Jie Qu ◽  
Yi Chun Lu ◽  
Vladimir E. Bondarenko ◽  
Shimin Wang ◽  
...  
Keyword(s):  
Steady State ◽  
Interacting Protein ◽  
Voltage Gated ◽  
Time To Peak ◽  
Kv Channel ◽  
Closed State ◽  
Channel Inactivation ◽  
Recovery From Inactivation

Voltage-gated K+ channels exist in vivo as multiprotein complexes made up of pore-forming and ancillary subunits. To further our understanding of the role of a dipeptidyl peptidase-related ancillary subunit, DPP10, we expressed it with Kv4.3 and Kv1.4, two channels responsible for fast-inactivating K+ currents. Previously, DPP10 has been shown to effect Kv4 channels. However, Kv1.4, when expressed with DPP10, showed many of the same effects as Kv4.3, such as faster time to peak current and negative shifts in the half-inactivation potential of steady-state activation and inactivation. The exception was recovery from inactivation, which is slowed by DPP10. DPP10 expressed with Kv4.3 caused negative shifts in both steady-state activation and inactivation of Kv4.3, but no significant shifts were detected when DPP10 was expressed with Kv4.3 + KChIP2b (Kv channel interacting protein). DPP10 and KChIP2b had different effects on closed-state inactivation. At −60 mV, KChIP2b nearly abolishes closed-state inactivation in Kv4.3, whereas it developed to a much greater extent in the presence of DPP10. Finally, expression of a DPP10 mutant consisting of its transmembrane and cytoplasmic 58 amino acids resulted in effects on Kv4.3 gating that were nearly identical to those of wild-type DPP10. These data show that DPP10 and KChIP2b both modulate Kv4.3 inactivation but that their primary effects are on different inactivation states. Thus DPP10 may be a general modulator of voltage-gated K+ channel inactivation; understanding its mechanism of action may lead to deeper understanding of the inactivation of a broad range of K+ channels.

PERIPHERAL NERVE REGENERATION THROUGH NERVE GUIDES FILLED WITH BILOBALIDE AND SCHWANN CELLS

2006 ◽  
Vol 18 (01) ◽  
pp. 8-12
Author(s):  
MING-CHIN LU ◽  
YUNG-HISEN CHANG ◽  
LEIH-CHIH CHIANG ◽  
HAI-TING WANG ◽  
CHUN-YUAN CHENG ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Chinese Medicine ◽  
Sciatic Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
New Approach ◽  
Nerve Guides ◽  
Growth Promoting

The present study provides in vivo trials of silicone rubber chambers filled with different concentrations of bilobalide (0, 50, 100, 200, 400 μM) and Schwann cells (1.5 × 105 cell/ml) in a 1:1 volumetric addition to bridge a 15 mm sciatic nerve defect in rats. At the conclusion of 8 weeks, histological technique was used to evaluate the functional recovery of the nerve. In the groups receiving the Schwann cells and bilobalide at 50, 100, 200 and 400 μM, 44% (4 of 9, one died during experiment), 50% (5 of 10), 30% (3 of 10), and 60% (6 of 10) of the animals exhibiting a regenerated nerve cable across the 15-mm gap, respectively. In comparison, 50% (5 of 10) of the animals in the group with Schwann cells only showed such regenerated nerve cables. Although the adding of bilobalide did not promote the nerve growth-promoting capability of Schwann cells in the nerve guides, the techniques we used in this study provided a new approach combining Chinese medicine and tissue engineering to nerve regeneration.

Inhibition of voltage-gated K+ channels in dendritic cells by rapamycin

2010 ◽  
Vol 299 (6) ◽  
pp. C1379-C1385 ◽  
Author(s):  
Leonid Tyan ◽  
Mentor Sopjani ◽  
Miribane Dërmaku-Sopjani ◽  
Evi Schmid ◽  
Wenting Yang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Xenopus Oocytes ◽  
Statistical Significance ◽  
Immunosuppressive Drug ◽  
Channel Activity ◽  
Voltage Gated ◽  
Kv Channel ◽  
Kv Channels ◽  
Channel Inactivation ◽  
Kv1.3 Channel

Rapamycin, an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR), is a widely used immunosuppressive drug. Rapamycin affects the function of dendritic cells (DCs), antigen-presenting cells participating in the initiation of primary immune responses and the establishment of immunological memory. Voltage-gated K+ (Kv) channels are expressed in and impact on the function of DCs. The present study explored whether rapamycin influences Kv channels in DCs. To this end, DCs were isolated from murine bone marrow and ion channel activity was determined by whole cell patch clamp. To more directly analyze an effect of mTOR on Kv channel activity, Kv1.3 and Kv1.5 were expressed in Xenopus oocytes with or without the additional expression of mTOR and voltage-gated currents were determined by dual-electrode voltage clamp. As a result, preincubation with rapamycin (0–50 nM) led to a gradual decline of Kv currents in DCs, reaching statistical significance within 6 h and 50 nM of rapamycin. Rapamycin accelerated Kv channel inactivation. Coexpression of mTOR upregulated Kv1.3 and Kv1.5 currents in Xenopus oocytes. Furthermore, mTOR accelerated Kv1.3 channel activation and slowed down Kv1.3 channel inactivation. In conclusion, mTOR stimulates Kv channels, an effect contributing to the immunomodulating properties of rapamycin in DCs.

scholarly journals The Amyloid Precursor Protein C99 Fragment Modulates Voltage-Gated Potassium Channels.

2021 ◽  
Vol 55 (S3) ◽  
pp. 157-170
Keyword(s):  
Amyloid Precursor Protein ◽  
Protein Interactions ◽  
Precursor Protein ◽  
Xenopus Laevis Oocytes ◽  
Cellular Functions ◽  
Voltage Gated ◽  
Adult Rat ◽  
Kv Channel ◽  
Kv Channels

BACKGROUND/AIMS: The Amyloid Precursor Protein (APP) is involved in the regulation of multiple cellular functions via protein-protein interactions and has been most studied with respect to Alzheimer's disease (AD). Abnormal processing of the single transmembrane-spanning C99 fragment of APP contributes to the formation of amyloid plaques, which are causally related to AD. Pathological C99 accumulation is thought to associate with early cognitive defects in AD. Here, unexpectedly, sequence analysis revealed that C99 exhibits 24% sequence identity with the KCNE1 voltage-gated potassium (Kv) channel β subunit, comparable to the identity between KCNE1 and KCNE2-5 (21-30%). This suggested the possibility of C99 regulating Kv channels. METHODS: We quantified the effects of C99 on Kv channel function, using electrophysiological analysis of subunits expressed in Xenopus laevis oocytes, biochemical and immunofluorescence techniques. RESULTS: C99 isoform-selectively inhibited (by 30-80%) activity of a range of Kv channels. Among the KCNQ (Kv7) family, C99 isoform-selectively inhibited, shifted the voltage dependence and/or slowed activation of KCNQ2, KCNQ3, KCNQ2/3 and KCNQ5, with no effects on KCNQ1, KCNQ1-KCNE1 or KCNQ4. C99/APP co-localized with KCNQ2 and KCNQ3 in adult rat sciatic nerve nodes of Ranvier. Both C99 and full-length APP co-immunoprecipitated with KCNQ2 in vitro, yet unlike C99, APP only weakly affected KCNQ2/3 activity. Finally, C99 altered the effects on KCNQ2/3 function of inhibitors tetraethylammounium and XE991, but not openers retigabine and ICA27243.

scholarly journals Not so optimal: The evolution of mutual information in potassium voltage-gated channels

2020 ◽  
Author(s):  
Alejandra Durán ◽  
Sarah Marzen
Keyword(s):  
Information Theory ◽  
Mutual Information ◽  
Statistical Mechanics ◽  
Essential Role ◽  
Gating Current ◽  
Voltage Gated ◽  
Kv Channel ◽  
Ionic Concentrations ◽  
Kv Channels ◽  
Voltage Gated Channels

AbstractPotassium voltage-gated (Kv) channels need to detect and respond to rapidly changing ionic concentrations in their environment. With an essential role in regulating electric signaling, they would be expected to be optimal sensors that evolved to predict the ionic concentrations. To explore these assumptions, we use statistical mechanics in conjunction with information theory to model how animal Kv channels respond to changes in potassium concentrations in their environment. By estimating mutual information in representative Kv channel types across a variety of environments, we find two things. First, under a wide variety of environments, there is an optimal gating current that maximizes mutual information between the sensor and the environment. Second, as Kv channels evolved, they have moved towards decreasing mutual information with the environment. This either suggests that Kv channels do not need to act as sensors of their environment or that Kv channels have other functionalities that interfere with their role as sensors of their environment.

Gene transcription of brain voltage-gated potassium channels is reversibly regulated by oxygen supply

2003 ◽  
Vol 285 (6) ◽  
pp. R1317-R1321 ◽  
Author(s):  
Howard M. Prentice ◽  
Sarah L. Milton ◽  
Daniela Scheurle ◽  
Peter L. Lutz
Keyword(s):  
Potassium Channels ◽  
Oxygen Supply ◽  
Brain Activity ◽  
Acute Hypoxia ◽  
Mrna Levels ◽  
Voltage Gated ◽  
Kv Channel ◽  
Kv Channels ◽  
Voltage Dependent ◽  
Channel Expression

Voltage-dependent potassium channels (Kv channels) are important determinants of brain electrical activity. Hypoxia may be an important modifier, because several voltage-gated K+ channels are reversibly blocked by acute hypoxia and are thought to act as oxygen sensors. Here we show, using the anoxia-tolerant turtle brain ( Trachemys scripta) as a model, that brain Kv1 channel transcription is reversibly regulated by oxygen supply. We found that in turtle brains exposed to 4-h anoxia Kv1 transcripts were reduced to 18.5% of normoxic levels. Kv1 channel mRNA levels were restored to normal within 4 h of subsequent reoxygenation. Our results provide clear evidence that brain Kv channel expression is sensitive to oxygen supply and indicate an important mechanism that matches brain activity to oxygen supply.

scholarly journals Voltage-gated potassium channel blocker 4-aminopyridine induces glioma cell apoptosis by reducing expression of microRNA-10b-5p

2018 ◽  
Vol 29 (9) ◽  
pp. 1125-1136 ◽  
Author(s):  
Qin Ru ◽  
Wei-ling Li ◽  
Qi Xiong ◽  
Lin Chen ◽  
Xiang Tian ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Channel Blocker ◽  
Glioma Cells ◽  
Current Data ◽  
Promoting Effect ◽  
Voltage Gated ◽  
Kv Channel ◽  
Kv Channels ◽  
Proliferation And Apoptosis ◽  
Related Proteins

Accumulating evidence has demonstrated that voltage-gated potassium channels (Kv channels) were associated with regulating cell proliferation and apoptosis in tumor cells. Our previous study proved that the Kv channel blocker 4-aminopyridine (4-AP) could inhibit cell proliferation and induce apoptosis in glioma. However, the precise mechanisms were not clear yet. MicroRNAs (miRNAs) are small noncoding RNAs that act as key mediators in the progression of tumor, so the aim of this study was to investigate the role of miRNAs in the apoptosis-promoting effect of 4-AP in glioma cells. Using a microRNA array, we found that 4-AP altered the miRNA expression in glioma cells, and the down-regulation of miR-10b-5p induced by 4-AP was verified by real-time PCR. Transfection of miR-10b-5p mimic significantly inhibited 4-AP–induced caspases activation and apoptosis. Moreover, we verified that apoptosis-related molecule Apaf-1 was the direct target of miR-10b-5p. Furthermore, miR-10b-5p mimic significantly inhibited 4-AP–induced up-regulation of Apaf-1 and its downstream apoptosis-related proteins, such as cleaved caspase-3. In conclusion, Kv channel blocker 4-AP may exert its anti-tumor effect by down-regulating the expression of miR-10b-5p and then raised expression of Apaf-1 and its downstream apoptosis-related proteins. Current data provide evidence that miRNAs play important roles in Kv channels-mediated cell proliferation and apoptosis.

scholarly journals Comparative Analysis of the Cell Fates of Induced Schwann Cells from Subcutaneous Fat Tissue and Naïve Schwann Cells in the Sciatic Nerve Injury Model

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Mingzi Zhang ◽  
Mei Hua Jiang ◽  
Dae-Wook Kim ◽  
Woosung Ahn ◽  
Eunkyung Chung ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cells ◽  
Subcutaneous Fat ◽  
Basal Membrane ◽  
Nerve Lesion ◽  
And Migration ◽  
Migration Capacity ◽  
And Function

Purpose. The fate and function of the induced Schwann cells (iSCs) like cells from adipose tissue have not been critically evaluated in vivo after transplantation. The objective of this study is to compare the fate of iSCs with naïve SCs (nSCs) after transplantation into the lesion sites of sciatic nerve, respectively. Methods. Adipose-derived stem cells from eGFP-expressing transgenic rat’s subcutaneous fat were induced to iSCs in vitro. iSCs were injected to the sciatic nerve lesion area after crush injury and the cells fate was comparatively analyzed with that of nSCs from the same rat. Results. At 12 weeks after transplantation, nSCs were detected only in the restricted area of cell transplantation site but iSCs were widely distributed all over the sciatic nerve. Based on double fluorescence observations, both iSCs and naïve ones were colocalized with P0-expressing myelin sheath, outbound by laminin-expressing basal membrane, and terminated at contactin-associated protein-expressing doublets. However, some of iSCs were also differentiated to the fibrocyte/fibroblast-like cells. In the histological analysis of repaired sciatic nerves, axon density was higher in iSC-received group than in the nSCs group and normal sciatic nerve. Conclusion. iSCs induced from subcutaneous fat tissues have higher engraftment and migration capacity than nSCs.

scholarly journals A unique mechanism of inactivation gating of the Kv channel family member Kv7.1 and its modulation by PIP2 and calmodulin

2020 ◽  
Vol 6 (51) ◽  
pp. eabd6922
Author(s):  
Maya Lipinsky ◽  
William Sam Tobelaim ◽  
Asher Peretz ◽  
Luba Simhaev ◽  
Adva Yeheskel ◽  
...  
Keyword(s):  
Family Member ◽  
Selectivity Filter ◽  
Wild Type ◽  
Voltage Gated ◽  
Kv Channel ◽  
Kv Channels ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Inactivation Gating ◽  
Unique Mechanism

Inactivation of voltage-gated K+ (Kv) channels mostly occurs by fast N-type or/and slow C-type mechanisms. Here, we characterized a unique mechanism of inactivation gating comprising two inactivation states in a member of the Kv channel superfamily, Kv7.1. Removal of external Ca2+ in wild-type Kv7.1 channels produced a large, voltage-dependent inactivation, which differed from N- or C-type mechanisms. Glu295 and Asp317 located, respectively, in the turret and pore entrance are involved in Ca2+ coordination, allowing Asp317 to form H-bonding with the pore helix Trp304, which stabilizes the selectivity filter and prevents inactivation. Phosphatidylinositol 4,5-bisphosphate (PIP2) and Ca2+-calmodulin prevented Kv7.1 inactivation triggered by Ca2+-free external solutions, where Ser182 at the S2-S3 linker relays the calmodulin signal from its inner boundary to the external pore to allow proper channel conduction. Thus, we revealed a unique mechanism of inactivation gating in Kv7.1, exquisitely controlled by external Ca2+ and allosterically coupled by internal PIP2 and Ca2+-calmodulin.

Sign in / Sign up

Export Citation Format

Share Document