scholarly journals Correction: Cotella et al., Toxic Role of K+ Channel Oxidation in Mammalian Brain

2012 ◽  
Vol 32 (27) ◽  
pp. 9449-9449
Keyword(s):  
Mammalian Brain ◽  
K Channel

scholarly journals Kv2.1 mediates spatial and functional coupling of L-type calcium channels and ryanodine receptors in mammalian neurons

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Nicholas C Vierra ◽  
Michael Kirmiz ◽  
Deborah van der List ◽  
L Fernando Santana ◽  
James S Trimmer
Keyword(s):  
Ryanodine Receptors ◽  
Spatial Proximity ◽  
Mammalian Brain ◽  
K Channel ◽  
Functional Coupling ◽  
Brain Neurons ◽  
Close Spatial Proximity ◽  
Unique Mechanism ◽  
Ca2 Channels

The voltage-gated K+ channel Kv2.1 serves a major structural role in the soma and proximal dendrites of mammalian brain neurons, tethering the plasma membrane (PM) to endoplasmic reticulum (ER). Although Kv2.1 clustering at neuronal ER-PM junctions (EPJs) is tightly regulated and highly conserved, its function remains unclear. By identifying and evaluating proteins in close spatial proximity to Kv2.1-containing EPJs, we discovered that a significant role of Kv2.1 at EPJs is to promote the clustering and functional coupling of PM L-type Ca2+ channels (LTCCs) to ryanodine receptor (RyR) ER Ca2+ release channels. Kv2.1 clustering also unexpectedly enhanced LTCC opening at polarized membrane potentials. This enabled Kv2.1-LTCC-RyR triads to generate localized Ca2+ release events (i.e., Ca2+ sparks) independently of action potentials. Together, these findings uncover a novel mode of LTCC regulation and establish a unique mechanism whereby Kv2.1-associated EPJs provide a molecular platform for localized somatodendritic Ca2+ signals in mammalian brain neurons.

scholarly journals Toxic Role of K+ Channel Oxidation in Mammalian Brain

2012 ◽  
Vol 32 (12) ◽  
pp. 4133-4144 ◽  
Author(s):  
D. Cotella ◽  
B. Hernandez-Enriquez ◽  
X. Wu ◽  
R. Li ◽  
Z. Pan ◽  
...  
Keyword(s):  
Mammalian Brain ◽  
K Channel

Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit carotid artery to NO

1995 ◽  
Vol 269 (3) ◽  
pp. H805-H811 ◽  
Author(s):  
S. Najibi ◽  
R. A. Cohen
Keyword(s):  
Carotid Artery ◽  
Sodium Nitroprusside ◽  
Channel Blocker ◽  
Isometric Tension ◽  
K Channel ◽  
K Channels ◽  
Rabbit Carotid Artery ◽  
Cyclic Monophosphate ◽  
Endothelium Dependent Relaxation

Endothelium-dependent relaxations to acetylcholine remain normal in the carotid artery of hypercholesterolemic rabbits, but unlike endothelium-dependent relaxations of normal rabbits, they are inhibited by charybdotoxin, a specific blocker of Ca(2+)-dependent K+ channels. Because nitric oxide (NO) is the mediator of endothelium-dependent relaxation and can activate Ca(2+)-dependent K+ channels directly or via guanosine 3',5'-cyclic monophosphate, the present study investigated the role of Ca(2+)-dependent K+ channels in relaxations caused by NO, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Brc-GMP) in hypercholesterolemic rabbit carotid artery. Isometric tension was measured in rabbit carotid artery denuded of endothelium from normal and hypercholesterolemic rabbits which were fed 0.5% cholesterol for 12 wk. Under control conditions, relaxations to all agents were similar in normal and hypercholesterolemic rabbit arteries. Charybdotoxin had no significant effect on relaxations of normal arteries to NO, sodium nitroprusside, or 8-BrcGMP, but the Ca(2+)-dependent K+ channel blocker significantly inhibited the relaxations caused by each of these agents in the arteries from hypercholesterolemic rabbits. By contrast, relaxations to the calcium channel blocker nifedipine were potentiated to a similar extent by charybdotoxin in both groups. In addition, arteries from hypercholesterolemic rabbits relaxed less than normal to sodium nitroprusside when contracted with depolarizing potassium solution. These results indicate that although nitrovasodilator relaxations are normal in the hypercholesterolemic rabbit carotid artery, they are mediated differently, and to a greater extent, by Ca(2+)-dependent K+ channels. These data also suggest that K+ channel-independent mechanism(s) are impaired in hypercholesterolemia.

scholarly journals Calnexin revealed as an ether-a-go-go chaperone by getting mutant worms up and going

2018 ◽  
Vol 150 (8) ◽  
pp. 1059-1061
Author(s):  
Jonathan T. Pierce
Keyword(s):  
Ion Channels ◽  
Dynamic Control ◽  
Cell Types ◽  
K Channel ◽  
Membrane Domains ◽  
Excitable Cells ◽  
Patch Clamp Recording ◽  
Cell Excitability ◽  
Distinct Membrane

The role of ion channels in cell excitability was first revealed in a series of voltage clamp experiments by Hodgkin and Huxley in the 1950s. However, it was not until the 1970s that patch-clamp recording ushered in a revolution that allowed physiologists to witness how ion channels flicker open and closed at angstrom scale and with microsecond resolution. The unexpectedly tight seal made by the patch pipette in the whole-cell configuration later allowed molecular biologists to suck up the insides of identified cells to unveil their unique molecular contents. By refining these techniques, researchers have scrutinized the surface and contents of excitable cells in detail over the past few decades. However, these powerful approaches do not discern which molecules are responsible for the dynamic control of the genesis, abundance, and subcellular localization of ion channels. In this dark territory, teams of unknown and poorly understood molecules guide specific ion channels through translation, folding, and modification, and then they shuttle them toward and away from distinct membrane domains via different subcellular routes. A central challenge in understanding these processes is the likelihood that these diverse regulatory molecules may be specific to ion channel subtypes, cell types, and circumstance. In work described in this issue, Bai et al. (2018. J. Gen. Physiol. https://doi.org/10.1085/jgp.201812025) begin to shed light on the biogenesis of UNC-103, a K+ channel found in Caenorhabditis elegans.

scholarly journals Potential role of luminal potassium in tubuloglomerular feedback.

1997 ◽  
Vol 8 (12) ◽  
pp. 1831-1837 ◽  
Author(s):  
V Vallon ◽  
H Osswald ◽  
R C Blantz ◽  
S Thomson
Keyword(s):  
Potential Role ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
K Channel ◽  
Thick Ascending Limb ◽  
Retrograde Perfusion ◽  
Luminal Membrane ◽  
K Concentration ◽  
Tubular Flow

Transport through the Na+-2Cl(-)-K+ cotransporter in the luminal membrane of macula densa cells is considered critical for tubuloglomerular feedback (TGF). Although various studies could support the importance of luminal Na+ and Cl-, the role of luminal K+ in TGF has not been thoroughly addressed. The study presented here examines this issue in nephrons with superficial glomeruli of anesthetized male Munich-Wistar-Frömter rats. Ambient Na+ concentration in early distal tubular fluid was approximately 22 mM, suggesting collection sites relatively close to the macula densa segment. First, it was found that ambient early distal tubular K+ concentration is approximately 1.3 mM, i.e., close to the K+ affinity of the Na+-2Cl(-)-K+ cotransporter in the thick ascending limb. Second, it was observed that a change in late proximal tubular flow rate, i.e., a maneuver that is known to induce a TGF response, significantly alters early distal tubular K+ concentration. Third, previous experiments failed to show an inhibition in TGF response during retrograde perfusion of the macula densa with K+-free solutions. Because of a potential K+ influx into the lumen between the perfusion site and the macula densa, however, the K+ channel blocker U37883A was added to the K+-free perfusate. TGF response was assessed as the fall in nephron filtration rate in response to retrograde perfusion of the macula densa segment from early distal tubular site. It was observed that luminal U37883A (100 microM) significantly attenuated TGF. Because adding 5 mM KCl to the perfusate restored TGF in the presence of U37883A and because the inhibitory action of U37883A on tubular K+ secretion was confirmed, the effect of U37883A on TGF was most likely caused by inhibition of K+ influx into the perfused segment, which decreased luminal K+ concentration at the macula densa. The present findings support a potential role for luminal K+ in TGF, which is in accordance with a transmission of the TGF signal across the macula densa via Na+-2Cl(-)-K+ cotransporter.

scholarly journals The role of thickness inhomogeneities in hierarchical cortical folding

2020 ◽  
Author(s):  
Lucas da Costa Campos ◽  
Raphael Hornung ◽  
Gerhard Gompper ◽  
Jens Elgeti ◽  
Svenja Caspers
Keyword(s):  
Fetal Brain ◽  
Epileptic Seizures ◽  
Quantitative Model ◽  
Higher Order ◽  
Mammalian Brain ◽  
Cortical Folding ◽  
Differential Growth ◽  
The Brain ◽  
Short Life Expectancy

AbstractThe morphology of the mammalian brain cortex is highly folded. For long it has been known that specific patterns of folding are necessary for an optimally functioning brain. On the extremes, lissencephaly, a lack of folds in humans, and polymicrogyria, an overly folded brain, can lead to severe mental retardation, short life expectancy, epileptic seizures, and tetraplegia. The construction of a quantitative model on how and why these folds appear during the development of the brain is the first step in understanding the cause of these conditions. In recent years, there have been various attempts to understand and model the mechanisms of brain folding. Previous works have shown that mechanical instabilities play a crucial role in the formation of brain folds, and that the geometry of the fetal brain is one of the main factors in dictating the folding characteristics. However, modeling higher-order folding, one of the main characteristics of the highly gyrencephalic brain, has not been fully tackled. The effects of thickness inhomogeneity in the gyrogenesis of the mammalian brain are studied in silico. Finite-element simulations of rectangular slabs are performed. The slabs are divided into two distinct regions, where the outer layer mimics the gray matter, and the inner layer the underlying white matter. Differential growth is introduced by growing the top layer tangentially, while keeping the underlying layer untouched. The brain tissue is modeled as a neo-Hookean hyperelastic material. Simulations are performed with both, homogeneous and inhomogeneous cortical thickness. The homogeneous cortex is shown to fold into a single wavelength, as is common for bilayered materials, while the inhomogeneous cortex folds into more complex conformations. In the early stages of development of the inhomogeneous cortex, structures reminiscent of the deep sulci in the brain are obtained. As the cortex continues to develop, secondary undulations, which are shallower and more variable than the structures obtained in earlier gyrification stage emerge, reproducing well-known characteristics of higher-order folding in the mammalian, and particularly the human, brain.

Molecular site for nucleotide binding on an ATP-sensitive renal K+ channel (ROMK2)

1996 ◽  
Vol 271 (2) ◽  
pp. F275-F285 ◽  
Author(s):  
C. M. McNicholas ◽  
Y. Yang ◽  
G. Giebisch ◽  
S. C. Hebert
Keyword(s):  
Channel Gating ◽  
Direct Interaction ◽  
K Channel ◽  
Amino Terminus ◽  
Atp Binding Site ◽  
Gating Mechanism ◽  
Alternatively Spliced ◽  
Carboxy Terminal ◽  
Apical Membranes

ATP-sensitive, inwardly rectifying K+ channels are present in apical membranes of the distal nephron and play a major role in K+ recycling and secretion. The cloned renal K+ channel, ROMK1, is a candidate for the renal epithelial K+ channel, since it shares many functional characteristics with the native channel. Additionally, ROMK1 contains a putative carboxy-terminal ATP-binding site. Although ROMK1 channel activity could be reactivated by cytosolic Mg-ATP after rundown, the role of nucleotides in channel gating was less certain. We now show that an alternatively spliced transcript of the ROMK channel gene, ROMK2, which encodes a K+ channel with a truncated amino terminus, expresses an ATP-regulated and ATP-sensitive K+ channel (IKATP). Differences in the amino terminus of ROMK isoforms alters the sensitivity of the channel-gating mechanism to ATP. To test whether ATP sensitivity of renal IKATP is mediated by direct interaction of nucleotide, point mutation of specific residues within the ROMK2 phosphate loop (P-loop) were investigated. These either enhanced or attenuated the sensitivity to both activation and inhibition by Mg-ATP, thus demonstrating a direct interaction of nucleotide with the channel-forming polypeptide.

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