scholarly journals Aldosterone, SGK1, and ion channels in the kidney

2018 ◽  
Vol 132 (2) ◽  
pp. 173-183 ◽  
Author(s):  
William C. Valinsky ◽  
Rhian M. Touyz ◽  
Alvin Shrier
Keyword(s):  
Ion Channels ◽  
Mineralocorticoid Receptor ◽  
Hydroxysteroid Dehydrogenase ◽  
Surface Expression ◽  
Cation Channels ◽  
Distal Nephron ◽  
Common Cause ◽  
Nonselective Cation Channels ◽  
Strongly Connected ◽  
And Function

Hyperaldosteronism, a common cause of hypertension, is strongly connected to Na+, K+, and Mg2+ dysregulation. Owing to its steroidal structure, aldosterone is an active transcriptional modifier when bound to the mineralocorticoid receptor (MR) in cells expressing the enzyme 11β-hydroxysteroid dehydrogenase 2, such as those comprising the aldosterone-sensitive distal nephron (ASDN). One such up-regulated protein, the ubiquitous serum and glucocorticoid regulated kinase 1 (SGK1), has the capacity to modulate the surface expression and function of many classes of renal ion channels, including those that transport Na+ (ENaC), K+ (ROMK/BK), Ca2+ (TRPV4/5/6), Mg2+ (TRPM7/6), and Cl− (ClC-K, CFTR). Here, we discuss the mechanisms by which ASDN expressed channels are up-regulated by SGK1, while highlighting newly discovered pathways connecting aldosterone to nonselective cation channels that are permeable to Mg2+ (TRPM7) or Ca2+ (TRPV4).

scholarly journals Site-specific deacylation by ABHD17a controls BK channel splice variant activity

2020 ◽  
Vol 295 (49) ◽  
pp. 16487-16496 ◽  
Author(s):  
Heather McClafferty ◽  
Hamish Runciman ◽  
Michael J. Shipston
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Membrane Trafficking ◽  
Transmembrane Protein ◽  
Surface Expression ◽  
Bk Channels ◽  
Bk Channel ◽  
Site Specific ◽  
And Function ◽  
A Site

S-Acylation, the reversible post-translational lipid modification of proteins, is an important mechanism to control the properties and function of ion channels and other polytopic transmembrane proteins. However, although increasing evidence reveals the role of diverse acyl protein transferases (zDHHC) in controlling ion channel S-acylation, the acyl protein thioesterases that control ion channel deacylation are very poorly defined. Here we show that ABHD17a (α/β-hydrolase domain-containing protein 17a) deacylates the stress-regulated exon domain of large conductance voltage- and calcium-activated potassium (BK) channels inhibiting channel activity independently of effects on channel surface expression. Importantly, ABHD17a deacylates BK channels in a site-specific manner because it has no effect on the S-acylated S0–S1 domain conserved in all BK channels that controls membrane trafficking and is deacylated by the acyl protein thioesterase Lypla1. Thus, distinct S-acylated domains in the same polytopic transmembrane protein can be regulated by different acyl protein thioesterases revealing mechanisms for generating both specificity and diversity for these important enzymes to control the properties and functions of ion channels.

scholarly journals Cyclic Nucleotide-Gated Ion Channels

2002 ◽  
Vol 82 (3) ◽  
pp. 769-824 ◽  
Author(s):  
U. Benjamin Kaupp ◽  
Reinhard Seifert
Keyword(s):  
Ion Channels ◽  
Sensory Neurons ◽  
Cyclic Nucleotide ◽  
Cation Channels ◽  
Voltage Gated ◽  
Nonselective Cation Channels ◽  
Retinal Photoreceptors ◽  
Cng Channel ◽  
B Subunits ◽  
Gated Ion Channels

Cyclic nucleotide-gated (CNG) channels are nonselective cation channels first identified in retinal photoreceptors and olfactory sensory neurons (OSNs). They are opened by the direct binding of cyclic nucleotides, cAMP and cGMP. Although their activity shows very little voltage dependence, CNG channels belong to the superfamily of voltage-gated ion channels. Like their cousins the voltage-gated K+ channels, CNG channels form heterotetrameric complexes consisting of two or three different types of subunits. Six different genes encoding CNG channels, four A subunits (A1 to A4) and two B subunits (B1 and B3), give rise to three different channels in rod and cone photoreceptors and in OSNs. Important functional features of these channels, i.e., ligand sensitivity and selectivity, ion permeation, and gating, are determined by the subunit composition of the respective channel complex. The function of CNG channels has been firmly established in retinal photoreceptors and in OSNs. Studies on their presence in other sensory and nonsensory cells have produced mixed results, and their purported roles in neuronal pathfinding or synaptic plasticity are not as well understood as their role in sensory neurons. Similarly, the function of invertebrate homologs found in Caenorhabditis elegans, Drosophila,and Limulus is largely unknown, except for two subunits of C. elegans that play a role in chemosensation. CNG channels are nonselective cation channels that do not discriminate well between alkali ions and even pass divalent cations, in particular Ca2+. Ca2+ entry through CNG channels is important for both excitation and adaptation of sensory cells. CNG channel activity is modulated by Ca2+/calmodulin and by phosphorylation. Other factors may also be involved in channel regulation. Mutations in CNG channel genes give rise to retinal degeneration and color blindness. In particular, mutations in the A and B subunits of the CNG channel expressed in human cones cause various forms of complete and incomplete achromatopsia.

Regulation of ion channels by protein tyrosine phosphorylation

2001 ◽  
Vol 281 (5) ◽  
pp. H1835-H1862 ◽  
Author(s):  
Michael J. Davis ◽  
Xin Wu ◽  
Timothy R. Nurkiewicz ◽  
Junya Kawasaki ◽  
Peichun Gui ◽  
...  
Keyword(s):  
Ion Channels ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinases ◽  
Scaffolding Proteins ◽  
Ion Channel Regulation ◽  
Protein Tyrosine ◽  
Channel Regulation ◽  
Nonselective Cation Channels ◽  
And Function

Ion channels are regulated by protein phosphorylation and dephosphorylation of serine, threonine, and tyrosine residues. Evidence for the latter process, tyrosine phosphorylation, has increased substantially since this topic was last reviewed. In this review, we present a comprehensive summary and synthesis of the literature regarding the mechanism and function of ion channel regulation by protein tyrosine kinases and phosphatases. Coverage includes the majority of voltage-gated, ligand-gated, and second messenger-gated channels as well as several types of channels that have not yet been cloned, including store-operated Ca2+ channels, nonselective cation channels, and epithelial Na+ and Cl− channels. Additionally, we discuss the critical roles that channel-associated scaffolding proteins may play in localizing protein tyrosine kinases and phosphatases to the vicinity of ion channels.

The mineralocorticoid receptor discriminates aldosterone from glucocorticoids independently of the 11ß-hydroxysteroid dehydrogenase

1995 ◽  
Vol 18 (7) ◽  
pp. 576-579 ◽  
Author(s):  
M. Lombes ◽  
S. Kenouch ◽  
A. Souque ◽  
N. Farman ◽  
M. E. Rafestin-Oblin ◽  
...  
Keyword(s):  
Mineralocorticoid Receptor ◽  
Hydroxysteroid Dehydrogenase

Kinematic Design of Functional Nanoscale Mechanisms From Molecular Primitives

2021 ◽  
Author(s):  
Meysam T. Chorsi ◽  
Pouya Tavousi ◽  
Caitlyn Mundrane ◽  
Vitaliy Gorbatyuk ◽  
Kazem Kazerounian ◽  
...  
Keyword(s):  
Ion Channels ◽  
Range Of Motion ◽  
Systematic Approach ◽  
Design Space ◽  
Vital Role ◽  
Degree Of Freedom ◽  
Living Systems ◽  
Kinematic Design ◽  
Systematic Exploration ◽  
And Function

Abstract Natural nanomechanisms such as capillaries, neurotransmitters, and ion channels play a vital role in the living systems. But the design principles developed by nature through evolution are not well understood and, hence, not applicable to engineered nanomachines. Thus, the design of nanoscale mechanisms with prescribed functions remains a challenge. Here, we present a systematic approach based on established kinematics techniques to designing, analyzing, and controlling manufacturable nanomachines with prescribed mobility and function built from a finite but extendable number of available "molecular primitives." Our framework allows the systematic exploration of the design space of irreducibly simple nanomachines, built with prescribed motion specification by combining available nanocomponents into systems having constrained, and consequently controllable motions. We show that the proposed framework has allowed us to discover and verify a molecule in the form of a seven link, seven revolute (7R) close loop spatial linkage with mobility (degree of freedom) of one. Furthermore, our experiments exhibit the type and range of motion predicted by our simulations. Enhancing such a structure into functional nanomechanisms by exploiting and controlling their motions individually or as part of an ensemble could galvanize development of the multitude of engineering, scientific, medical, and consumer applications that can benefit from engineered nanomachines.

scholarly journals Cellular distribution and function of ion channels involved in transport processes in rat tracheal epithelium

2017 ◽  
Vol 5 (12) ◽  
pp. e13290 ◽  
Author(s):  
Anne Hahn ◽  
Johannes Faulhaber ◽  
Lalita Srisawang ◽  
Andreas Stortz ◽  
Johanna J Salomon ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transport Processes ◽  
Tracheal Epithelium ◽  
Cellular Distribution ◽  
And Function

Inhibition of hypoxic pulmonary vasoconstriction by antagonists of store-operated Ca2+ and nonselective cation channels

2005 ◽  
Vol 289 (1) ◽  
pp. L5-L13 ◽  
Author(s):  
Letitia Weigand ◽  
Joshua Foxson ◽  
Jian Wang ◽  
Larissa A. Shimoda ◽  
J. T. Sylvester
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Pulmonary Arteries ◽  
Cation Channels ◽  
Pulmonary Vasoconstriction ◽  
Nonselective Cation Channels ◽  
Pressor Responses ◽  
Intracellular Ca ◽  
Pulmonary Arterial

Previous studies indicated that acute hypoxia increased intracellular Ca2+ concentration ([Ca2+]i), Ca2+ influx, and capacitative Ca2+ entry (CCE) through store-operated Ca2+ channels (SOCC) in smooth muscle cells from distal pulmonary arteries (PASMC), which are thought to be a major locus of hypoxic pulmonary vasoconstriction (HPV). Moreover, these effects were blocked by Ca2+-free conditions and antagonists of SOCC and nonselective cation channels (NSCC). To test the hypothesis that in vivo HPV requires CCE, we measured the effects of SOCC/NSCC antagonists (SKF-96365, NiCl2, and LaCl3) on pulmonary arterial pressor responses to 2% O2 and high-KCl concentrations in isolated rat lungs. At concentrations that blocked CCE and [Ca2+]i responses to hypoxia in PASMC, SKF-96365 and NiCl2 prevented and reversed HPV but did not alter pressor responses to KCl. At 10 μM, LaCl3 had similar effects, but higher concentrations (30 and 100 μM) caused vasoconstriction during normoxia and potentiated HPV, indicating actions other than SOCC blockade. Ca2+-free perfusate and the voltage-operated Ca2+ channel (VOCC) antagonist nifedipine were potent inhibitors of pressor responses to both hypoxia and KCl. We conclude that HPV required influx of Ca2+ through both SOCC and VOCC. This dual requirement and virtual abolition of HPV by either SOCC or VOCC antagonists suggests that neither channel provided enough Ca2+ on its own to trigger PASMC contraction and/or that during hypoxia, SOCC-dependent depolarization caused secondary activation of VOCC.

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