Krupinski T et al. (2009) Physiology (Bethesda) "Unexpected roles of the Na-K-ATPase and other ion transporters in cell junctions and tubulogenesis."

Beitel GJ, Krupinski T

[Physiology (Bethesda), 2009]

Recent work shows that transport-independent as well as transport-dependent functions of ion transporters, and in particular the Na-K-ATPase, are required for formation and maintenance of several intercellular junctions. Furthermore, these junctional and other nonjunctional functions of ion transporters contribute to development of epithelial tubes. Here, we consider what has been learned about the roles of ion pumps in formation of junctions and epithelial tubes in mammals, zebrafish, Drosophila, and C. elegans. We propose that asymmetric association of the Na-K-ATPase with cell junctions early in metazoan evolution enabled vectorial transcellular ion transport and control of intraorganismal environment. Ion transport-independent functions of the Na-K-ATPase arose as junctional complexes evolved.

Garcia-Anoveros J et al. (1996) Curr Biol "Touch at the molecular level. Mechanosensation."

Corey DP, Garcia-Anoveros J

[Curr Biol, 1996]

The cloning of genes needed for gentle-touch sensitivity in the nematode Caenorhabditis elegans has provided new molecular details about a proposed mechanosensory ion channel complex.

Clapham DE et al. (2003) Pharmacol Rev "International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels."

Clapham DE, Montell C, Schultz G, Julius D

[Pharmacol Rev, 2003]

The transient receptor potential (TRP) proteins are six transmembrane-containing subunits that combine to form cation-selective ion channels. TRP channels are present in yeast, Drosophila, Caenorhabditis elegans, and mammals. They are widely distributed and sense local changes in stimuli ranging from light to temperature and osmolarity. Mammals contain at least 22 distinct genes encoding these ion channels. This summary article presents an overview of the molecular relationships among the TRP channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium of Voltage-Gated Ion Channels. The complete Compendium, including data tables for each member of the TRP channel family, can be found at http://www.iuphar-db.org/iuphar-ic/.

Palmer ML et al. (2006) Cell Biochem Biophys "RNA interference and ion channel physiology."

Palmer ML, Fahrenkrug SC, O'grady SM

[Cell Biochem Biophys, 2006]

RNA interference (RNAi), through expression of small, double-stranded RNAs or short hairpin RNAs, produces sequence-specific mRNA degradation and decreased gene expression. Since its discovery in 1998 (Fire et al., 1998, Nature 391, 806-811), RNAi has rapidly become one of the most widely used technologies for exploring gene function in eukaryotic cells. Although the topic of RNAi has been the subject of a large number of excellent reviews, the focus of this article is on its application to the study of ion channel physiology in animal cells. In this regard, RNAi has provided definitive identification of ion channel subtypes responsible for both basal and stimulated ion conduction across the plasma membrane of several cell types. The approach has been particularly effective in identifying and establishing the contribution of auxiliary subunits and regulatory proteins to the overall function of ion channel complexes. Moreover, selective knockdown of ion channel expression has been a valuable means of demonstrating roles in the development of specific cell domains and in the normal growth of certain cell types. In this review, a brief description of the general mechanism of RNAi is presented, followed by a discussion of some important considerations for the in vitro application of this technology and in producing transgenic animals as models for human disease. We then describe several examples of where RNAi has been used to investigate the physiological role of ion channels in cells from model organisms (Caenorhabditis elegans and Drosophila melanogaster) and in mammalian cells.

Tavernarakis N et al. (2001) Ann N Y Acad Sci "Degenerins. At the core of the metazoan mechanotransducer?"

Tavernarakis N, Driscoll M

[Ann N Y Acad Sci, 2001]

Mechanosensory signaling, believed to be mediated by mechanically gated ion channels, constitutes the basis for the senses of touch and hearing, and contributes fundamentally to the development and homeostasis of all organisms. Despite this profound importance in biology, little is known of the molecular identities or functional requirements of mechanically gated ion channels. Genetic analyses of touch sensation and locomotion in Caenorhabditis elegans have implicated a new class of ion channels, the degenerins (DEG) in nematode mechanotransduction. Related fly and vertebrate proteins, the epithelial sodium channel (ENaC) family, have been implicated in several important processes, including transduction of mechanical stimuli, pain sensation, gametogenesis, sodium reabsorption, and blood pressure regulation. Still-to-be-discovered DEG/ENaC proteins may compose the core of the elusive human mechanotransducer.

Folgering JH et al. (2008) Prog Biophys Mol Biol "Molecular basis of the mammalian pressure-sensitive ion channels: focus on vascular mechanotransduction."

Dedman A, Patel A, Delmas P, Honore E, Folgering JH, Sharif-Naeini R

[Prog Biophys Mol Biol, 2008]

Mechano-gated ion channels are implicated in a variety of neurosensory functions ranging from touch sensitivity to hearing. In the heart, rhythm disturbance subsequent to mechanical effects is also associated with the activation of stretch-sensitive ion channels. Arterial autoregulation in response to hemodynamic stimuli, a vital process required for protection against hypertension-induced injury, is similarly dependent on the activity of force-sensitive ion channels. Seminal work in prokaryotes and invertebrates, including the nematode Caenorhabditis elegans and the fruit fly drosophila, greatly helped to identify the molecular basis of volume regulation, hearing and touch sensitivity. In mammals, more recent findings have indicated that members of several structural family of ion channels, namely the transient receptor potential (TRP) channels, the amiloride-sensitive ENaC/ASIC channels and the potassium channels K(2P) and K(ir) are involved in cellular mechanotransduction. In the present review, we will focus on the molecular and functional properties of these channel subunits and will emphasize on their role in the pressure-dependent arterial myogenic constriction and the flow-mediated vasodilation.

Sheng Y et al. (2017) J Cell Physiol "Membrane Ion Channels and Receptors in Animal Lifespan Modulation."

Kang L, Tang L, Xiao R, Sheng Y

[J Cell Physiol, 2017]

Acting in the interfaces between environment and membrane compartments, membrane ion channels and receptors transduce various physical and chemical cues into downstream signaling events. Not surprisingly, these membrane proteins play essential roles in a wide range of cellular processes such as sensory perception, synaptic transmission, cellular growth and development, fate determination, and apoptosis. However, except insulin and insulin-like growth factor receptors, the functions of membrane receptors in animal lifespan modulation have not been well appreciated. On the other hand, although ion channels are popular therapeutic targets for many age-related diseases, their potential roles in aging itself are largely neglected. In this review, we will discuss our current understanding of the conserved functions and mechanisms of membrane ion channels and receptors in the modulation of lifespan across multiple species including C. elegans, Drosophila, mouse, and human. This article is protected by copyright. All rights reserved.

Waldmann R et al. (1998) Curr Opin Neurobiol "H+-gated cation channels: nruonal acid sensors in the NaC/DEG family of ion channels."

Waldmann R, Lazdunski M

[Curr Opin Neurobiol, 1998]

Ion channels in the amiloride-sensitive Na+ channel/degenerin (NaC/DEG) family of cation channels have very diverse functions. They can be constitutively active (e.g. the epithelial Na+ channel), gated by a ligand (e.g. the peptide-gated channel FaNaC or H+-gated cation channels [ASICs]) or possibly activated by stretch (degenerins of Caenorhabditis elegans). Despite this functional diversity, the heterologous expressed channels share the following properties: permeability to Na+, inhibition by the diuretic amiloride and no voltage gating. This review will focus on recent advances in this ion channel family, with special emphasis on H+-gated cation channels.

Martin RJ et al. (2012) Trends Parasitol "Levamisole receptors: a second awakening."

Neveu C, Robertson AP, Martin RJ, Charvet CL, Beech RN, Buxton SK

[Trends Parasitol, 2012]

Levamisole and pyrantel are old (1965) but useful anthelmintics that selectively activate nematode acetylcholine ion channel receptors; they are used to treat roundworm infections in humans and animals. Interest in their actions has surged, giving rise to new knowledge and technical advances, including an ability to reconstitute receptors that reveal more details of modes of action/resistance. We now know that the receptors are plastic and may form diverse species-dependent subtypes of receptor with different sensitivities to individual cholinergic anthelmintics. Understanding the biology of the levamisole receptors is expected to inform other studies on anthelmintics (ivermectin and emodepside) that act on ion channels.

Bargmann CI (1998) Science "Neurobiology of the Caenorhabditis elegans genome."

Bargmann CI

[Science, 1998]

Neurotransmitter receptors, neurotransmitter synthesis and release pathways, and heterotrimeric GTP-binding protein (G protein)-coupled second messenger pathways are highly conserved between Caenorhabditis elegans and mammals, but gap junctions and chemosensory receptors have independent origins in vertebrates and nematodes. Most ion channels are similar to vertebrate channels but there are no predicted voltage-activated sodium channels. The C. elegans genome encodes at least 80 potassium channels, 90 neurotransmitter-gated ion channels, 50 peptide receptors, and up to 1000 orphan receptors that may be chemoreceptors. For many gene families, C. elegans has both conventional members and divergent outliers with weak homology to known genes; these outliers may provide insights into previously unknown functions of conserved protein families.