Two sites for adenine-nucleotide regulation of ATP-sensitive potassium channels in mouse pancreatic ?-cells and HIT cells

1992 ◽  
Vol 129 (3) ◽  
Author(s):  
WilliamF. Hopkins ◽  
Sahba Fatherazi ◽  
Bettina Peter-Riesch ◽  
BarbaraE. Corkey ◽  
DanielL. Cook
Keyword(s):  
Potassium Channels ◽  
Adenine Nucleotide ◽  
Pancreatic Cells ◽  
Nucleotide Regulation ◽  
Hit Cells

Nucleotide regulation of ATP sensitive potassium channels

1994 ◽  
Vol 28 (6) ◽  
pp. 746-753 ◽  
Author(s):  
A. Terzic ◽  
R. T Tung ◽  
Y. Kurachi
Keyword(s):  
Potassium Channels ◽  
Nucleotide Regulation

Structural insights into the mechanism of nucleotide regulation of pancreatic KATP channel

2021 ◽  
Author(s):  
Mengmeng Wang ◽  
Jing-Xiang Wu ◽  
Dian Ding ◽  
Xinli Duan ◽  
Songling Ma ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Katp Channel ◽  
Katp Channels ◽  
Activation Mechanism ◽  
Fundamental Properties ◽  
Closed State ◽  
Physiological Processes ◽  
Nucleotide Regulation ◽  
Atp Inhibition ◽  
Structural Insights

ATP-sensitive potassium channels (KATP) are metabolic sensors that convert the intracellular ATP/ADP ratio to the excitability of cells. They are involved in many physiological processes and implicated in several human diseases. Here we present the cryo-EM structures of the pancreatic KATP channel in both the closed state and the pre-open state, resolved in the same sample. The nucleotides bind at the inhibitory sites of the Kir6.2 channel in the closed state but not in the pre-open state. Structural comparisons reveal the mechanism for ATP inhibition and Mg-ADP activation, two fundamental properties of KATP channels. Moreover, the structure also uncovers the activation mechanism of diazoxide-type KATP openers.

scholarly journals Nucleotide regulation of heat-stable enterotoxin receptor binding and of guanylate cyclase activation

1992 ◽  
Vol 283 (3) ◽  
pp. 727-735 ◽  
Author(s):  
L C Katwa ◽  
C D Parker ◽  
J K Dybing ◽  
A A White
Keyword(s):  
Guanylate Cyclase ◽  
Single Phase ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Inhibitory Effects ◽  
Nucleotide Analogues ◽  
Heat Stable ◽  
Low Concentrations ◽  
Nucleotide Regulation ◽  
Guanylate Cyclase Activation

Certain nucleotides were found to regulate the binding of the Escherichia coli heat-stable enterotoxin (STa) to its receptor in pig intestinal brush border membranes. ATP and adenine nucleotide analogues inhibited 125I-STa binding, while guanine nucleotide analogues stimulated binding, with maximal effects at 0.5-1.0 mM. The strongest inhibitors were adenosine 5′-[beta gamma-imido]triphosphate (App[NH]p) (36%) and adenosine 5′-[beta-thio]diphosphate (ADP[S]) (41%). Inhibition did not require Mg2+, and was blocked by p-chloromercuribenzenesulphonate (PCMBS). Stimulation of binding required Mg2+, was not prevented by PCMBS and was maximal with GDP[S] (41%). While App[NH]p and MgGDP[S] appeared to be acting at different sites, they also interfered with each other. These nucleotides exerted only inhibitory effects on STa-stimulated guanylate cyclase activity, in contrast with the stimulatory effects of adenine nucleotides on atrial natriuretic peptide (ANP)-stimulated guanylate cyclase. Inhibition by low concentrations of MgApp[NH]p and MgATP was weaker above 0.1 mM, while MgGDP[S] and magnesium guanosine 5′-[gamma-thio]triphosphate (MgGTP[S]) inhibited in a single phase. Inhibition by MgApp[NH]p, at all concentrations, was competitive with the substrate (MgGTP), as was that by MgGDP[S] and MgGTP[S]. Whereas membrane guanylate cyclases usually show positively co-operative kinetics with respect to the substrate, STa-stimulated activity exhibited Michaelis-Menten kinetics with respect to MgGTP. This changed to positive co-operativity when Lubrol PX was the activator, or when the substrate was MnGTP. These results suggest the presence of both a regulatory and a catalytic nucleotide-binding site, which do not interact co-operatively with STa activation.

scholarly journals Metabolic Energy Sensing by Mammalian CLC Anion/Proton Exchangers

2019 ◽  
Author(s):  
Matthias Grieschat ◽  
Katharina Langschwager ◽  
Raul E. Guzman ◽  
Christoph Fahlke ◽  
Alexi K. Alekov
Keyword(s):  
Heterologous Expression ◽  
Protein C ◽  
Voltage Dependence ◽  
Adenine Nucleotide ◽  
Metabolic Energy ◽  
System Components ◽  
Nucleotide Regulation ◽  
Vesicular Transporters ◽  
Energy Sensing ◽  
Cbs Domains

AbstractMammalian CLC anion/proton exchangers control the pH and [Cl-] of the endolysosomal system, one of the major cellular nutrient uptake pathways. We explored the regulation of the vesicular transporters ClC-3, ClC-4, and ClC-5 by the adenylic system components ATP, ADP, and AMP. Using heterologous expression and whole-cell electrophysiology, we demonstrated that cytosolic ATP and ADP but not AMP and Mg2+-free ADP enhance CLC ion transport via binding to the protein C-terminal CBS domains. Biophysical investigations revealed that the effects depend on the delivery of intracellular protons into the CLC transport machinery and result from modified voltage-dependence and altered probability that CLC proteins undergo silent non-transporting cycles. Our findings demonstrate that the CLC CBS domains are able to serve as energy sensors by detecting changes in the cytosolic ATP/ADP/AMP equilibrium. The adenine nucleotide regulation of vesicular Cl-/H+ exchange creates a link between the activity of the endolysosomal system and the cellular metabolic state.

scholarly journals Visualizing Adenine Nucleotide Regulation of the KATP Channel

2018 ◽  
Vol 114 (3) ◽  
pp. 25a-26a
Author(s):  
Samuel G. Usher ◽  
Natascia Vedovato ◽  
Michael C. Puljung ◽  
Frances M. Ashcroft
Keyword(s):  
Katp Channel ◽  
Adenine Nucleotide ◽  
Nucleotide Regulation

Structural modifications of intercellular junctions.

1978 ◽  
Vol 36 (2) ◽  
pp. 330-331
Author(s):  
J. Metz ◽  
M. Merlo ◽  
W. G. Forssmann
Keyword(s):  
Gap Junctions ◽  
Intercellular Junctions ◽  
Cell Isolation ◽  
Extrahepatic Cholestasis ◽  
Structural Modifications ◽  
Pancreatic Duct Ligation ◽  
Pancreatic Cells ◽  
Duct Ligation ◽  
Thin Sectioning ◽  
And Function

Structure and function of intercellular junctions were studied under the electronmicroscope using conventional thin sectioning and freeze-etch replicas. Alterations of tight and gap junctions were analyzed 1. of exocrine pancreatic cells under cell isolation conditions and pancreatic duct ligation and 2. of hepatocytes during extrahepatic cholestasis.During the different steps of cell isolation of exocrine pancreatic cells, gradual changes of tight and gap junctions were observed. Tight junctions, which formed belt-like structures around the apex of control acinar cells in situ, subsequently diminished, became interrupted and were concentrated into macular areas (Fig. 1). Aggregations of membrane associated particles, which looked similar to gap junctions, were intermixed within tight junctional areas (Fig. 1). These structures continously disappeared in the last stages of the isolation procedure. The intercellular junctions were finally separated without destroying the integrity of the cell membrane, which was confirmed with porcion yellow, lanthanum chloride and horse radish peroxidase.

Structure of contact sites between the outer and inner mitochondrial membranes investigated by HVEM tomography

1996 ◽  
Vol 54 ◽  
pp. 966-967
Author(s):  
C.A. Mannella ◽  
K.F. Buttle ◽  
K.A. O‘Farrell ◽  
A. Leith ◽  
M. Marko
Keyword(s):  
Liver Mitochondrion ◽  
Adenine Nucleotide ◽  
Protein Complexes ◽  
Mitochondrial Membranes ◽  
Electron Microscopic ◽  
Contact Sites ◽  
Transmission Electron ◽  
Precursor Proteins ◽  
Membrane Contacts ◽  
And Function

Early transmission electron microscopy of plastic-embedded, thin-sectioned mitochondria indicated that there are numerous junctions between the outer and inner membranes of this organelle. More recent studies have suggested that the mitochondrial membrane contacts may be the site of protein complexes engaged in specialized functions, e.g., import of mitochondrial precursor proteins, adenine nucleotide channeling, and even intermembrane signalling. It has been suggested that the intermembrane contacts may be sites of membrane fusion involving non-bilayer lipid domains in the two membranes. However, despite growing interest in the nature and function of intramitochondrial contact sites, little is known about their structure.We are using electron microscopic tomography with the Albany HVEM to determine the internal organization of mitochondria. We have reconstructed a 0.6-μm section through an isolated, plasticembedded rat-liver mitochondrion by combining 123 projections collected by tilting (+/- 70°) around two perpendicular tilt axes. The resulting 3-D image has confirmed the basic inner-membrane organization inferred from lower-resolution reconstructions obtained from single-axis tomography.

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