scholarly journals The human two-pore channel 1 is modulated by cytosolic and luminal calcium

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura Lagostena ◽  
Margherita Festa ◽  
Michael Pusch ◽  
Armando Carpaneto
Keyword(s):  
Pore Channel ◽  
Luminal Calcium

How to Fluorescently Label the Potassium Channel: A Case in hERG

2020 ◽  
Vol 27 (18) ◽  
pp. 3046-3054
Author(s):  
Xiaomeng Zhang ◽  
Beilei Wang ◽  
Zhenzhen Liu ◽  
Yubin Zhou ◽  
Lupei Du
Keyword(s):  
Potassium Channel ◽  
Herg Channel ◽  
Pore Channel ◽  
Design Rationale ◽  
Related Gene ◽  
Open Conformation ◽  
Cardiac Action ◽  
Qt Syndrome ◽  
Herg Channels ◽  
Action Potential Repolarization

hERG (Human ether-a-go-go-related gene) potassium channel, which plays an essential role in cardiac action potential repolarization, is responsible for inherited and druginduced long QT syndrome. Recently, the Cryo-EM structure capturing the open conformation of hERG channel was determined, thus pushing the study on hERG channel at 3.8 Å resolution. This report focuses primarily on summarizing the design rationale and application of several fluorescent probes that target hERG channels, which enables dynamic and real-time monitoring of potassium pore channel affinity to further advance the understanding of the channels.

scholarly journals Endolysosomal Cation Channels and MITF in Melanocytes and Melanoma

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1021
Author(s):  
Carla Abrahamian ◽  
Christian Grimm
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Convincing Evidence ◽  
Signaling Cascades ◽  
Cation Channels ◽  
Pore Channel ◽  
Different Types ◽  
Canonical Wnt ◽  
The Relationship

Microphthalmia-associated transcription factor (MITF) is the principal transcription factor regulating pivotal processes in melanoma cell development, growth, survival, proliferation, differentiation and invasion. In recent years, convincing evidence has been provided attesting key roles of endolysosomal cation channels, specifically TPCs and TRPMLs, in cancer, including breast cancer, glioblastoma, bladder cancer, hepatocellular carcinoma and melanoma. In this review, we provide a gene expression profile of these channels in different types of cancers and decipher their roles, in particular the roles of two-pore channel 2 (TPC2) and TRPML1 in melanocytes and melanoma. We specifically discuss the signaling cascades regulating MITF and the relationship between endolysosomal cation channels, MAPK, canonical Wnt/GSK3 pathways and MITF.

scholarly journals Role of the Putative NAADP Receptor, Two-Pore Channel 2, in Ventricular Myocyte Responses to Isoproterenol

2010 ◽  
Vol 98 (3) ◽  
pp. 100a
Author(s):  
Laura C. Elson ◽  
William D. Owen ◽  
Arie R. Gafson ◽  
John Parrington ◽  
Antony Galione ◽  
...  
Keyword(s):  
Pore Channel ◽  
Ventricular Myocyte

scholarly journals Gating Competence of Constitutively Open CLC-0 Mutants Revealed by the Interaction with a Small Organic Inhibitor

2003 ◽  
Vol 122 (3) ◽  
pp. 295-306 ◽  
Author(s):  
Sonia Traverso ◽  
Laura Elia ◽  
Michael Pusch
Keyword(s):  
Chloride Channels ◽  
Bound State ◽  
Side Chain ◽  
Pore Channel ◽  
Kinetic Properties ◽  
Wild Type ◽  
High Affinity ◽  
Critical Residue ◽  
Fast Gating

Opening of CLC chloride channels is coupled to the translocation of the permeant anion. From the recent structure determination of bacterial CLC proteins in the closed and open configuration, a glutamate residue was hypothesized to form part of the Cl−-sensitive gate. The negatively charged side-chain of the glutamate was suggested to occlude the permeation pathway in the closed state, while opening of a single protopore of the double-pore channel would reflect mainly a movement of this side-chain toward the extracellular pore vestibule, with little rearrangement of the rest of the channel. Here we show that mutating this critical residue (Glu166) in the prototype Torpedo CLC-0 to alanine, serine, or lysine leads to constitutively open channels, whereas a mutation to aspartate strongly slowed down opening. Furthermore, we investigated the interaction of the small organic channel blocker p-chlorophenoxy-acetic acid (CPA) with the mutants E166A and E166S. Both mutants were strongly inhibited by CPA at negative voltages with a >200-fold larger affinity than for wild-type CLC-0 (apparent KD at −140 mV ∼4 μM). A three-state linear model with an open state, a low-affinity and a high-affinity CPA-bound state can quantitatively describe steady-state and kinetic properties of the CPA block. The parameters of the model and additional mutagenesis suggest that the high-affinity CPA-bound state is similar to the closed configuration of the protopore gate of wild-type CLC-0. In the E166A mutant the glutamate side chain that occludes the permeation pathway is absent. Thus, if gating consists only in movement of this side-chain the mutant E166A should not be able to assume a closed conformation. It may thus be that fast gating in CLC-0 is more complex than anticipated from the bacterial structures.

Comparison of calcium absorptive and secretory capacities of segments of intact or functionally resected intestine during normo-, hypo-, and hyper-calcemia

1994 ◽  
Vol 72 (7) ◽  
pp. 764-770 ◽  
Author(s):  
N. Krishnamra ◽  
K. Angkanaporn ◽  
T. Deenoi
Keyword(s):  
Calcium Absorption ◽  
Intestinal Secretion ◽  
Proximal Colon ◽  
Plasma Calcium ◽  
Proximal Jejunum ◽  
Proximal Small Intestine ◽  
Enhanced Secretion ◽  
Rate Of Absorption ◽  
Plasma Calcium Concentration ◽  
Luminal Calcium

Absorptive and secretory capacities of six in situ intestinal loops of equal length were compared under the same calcium load and calcemic condition. The highest rate of calcium absorption was found in duodenum, colon, and proximal jejunum when loops were filled with 0.3 mM calcium, and in duodenum and proximal jejunum when filled with 10 mM luminal calcium. Secretory rates were in the following order: duodenum, jejunum, proximal jejunum, cecum, ileum, and proximal colon. Absorption of 0.3 mM calcium was decreased in all but the cecum and colon during hypercalcemia, and in duodenum, proximal jejunum, and colon during thyroparathyroidectomy-induced hypocalcemia. In contrast, calcium secretion was directly related to plasma calcium concentration and the length of the intestine. Functional resection of any part met with a compensatory increase in calcium absorption by the remaining segments, with the exception of the resection of the distal ileum with the large bowel. In conclusion, proximal small intestine exhibited the highest rate of absorption and secretion, but functional resection of this or any part did not affect the overall calcium absorption if luminal calcium was 10 mM. Moreover, enhanced secretion and reduced absorption during hypercalcemia were beneficial with respect to plasma calcium regulation.Key words: calcium, hypercalcemia, hypocalcemia, intestinal absorption, intestinal secretion.

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