Ion channel regulation by G proteins

1995 ◽  
Vol 75 (4) ◽  
pp. 865-885 ◽  
Author(s):  
K. Wickman ◽  
D. E. Clapham
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
G Protein ◽  
G Proteins ◽  
Second Messengers ◽  
Channel Activity ◽  
Ion Channel Regulation ◽  
Protein Subunits ◽  
Channel Regulation ◽  
Intracellular Cascades

Ion channels are poised uniquely to initiate, mediate, or regulate such distinct cellular activities as action potential propagation, secretion, and gene transcription. In retrospect, it is not surprising that studies of ion channels have revealed considerable diversities in their primary structures, regulation, and expression. From a functional standpoint, the various mechanisms coopted by cells to regulate channel activity are particularly fascinating. Extracellular ligands, membrane potential, phosphorylation, ions themselves, and diffusible second messengers are all well-established regulators of ion channel activity. Heterotrimeric GTP-binding proteins (G proteins) mediate many of these types of ion channel regulation by stimulating or inhibiting phosphorylation pathways, initiating intracellular cascades leading to elevation of cytosolic Ca2+ or adenosine 3',5'-cyclic monophosphate levels, or by generating various lipid-derived compounds. In some cases, it seems that activated G protein subunits can interact directly with ion channels to elicit regulation. Although there is currently little direct biochemical evidence to support such a mechanism, it is the working hypothesis for the most-studied G protein-regulated ion channels.

Regulation of ion transport by oxidants

2013 ◽  
Vol 305 (9) ◽  
pp. L595-L603 ◽  
Author(s):  
Charles A. Downs ◽  
My N. Helms
Keyword(s):  
Oxidative Stress ◽  
Ion Channels ◽  
Ion Channel ◽  
Redox Regulation ◽  
Experimental Biology ◽  
Cellular Functions ◽  
Ion Channel Regulation ◽  
Channel Regulation ◽  
Made In

Ion channels perform a variety of cellular functions in lung epithelia. Oxidant- and antioxidant-mediated mechanisms (that is, redox regulation) of ion channels are areas of intense research. Significant progress has been made in our understanding of redox regulation of ion channels since the last Experimental Biology report in 2003. Advancements include: 1) identification of nonphagocytic NADPH oxidases as sources of regulated reactive species (RS) production in epithelia, 2) an understanding that excessive treatment with antioxidants can result in greater oxidative stress, and 3) characterization of novel RS signaling pathways that converge upon ion channel regulation. These advancements, as discussed at the 2013 Experimental Biology Meeting in Boston, MA, impact our understanding of oxidative stress in the lung, and, in particular, illustrate that the redox state has profound effects on ion channel and cellular function.

scholarly journals PIP2: A critical regulator of vascular ion channels hiding in plain sight

2020 ◽  
Vol 117 (34) ◽  
pp. 20378-20389 ◽  
Author(s):  
Osama F. Harraz ◽  
David Hill-Eubanks ◽  
Mark T. Nelson
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Intracellular Signaling ◽  
Vascular Function ◽  
Current Knowledge ◽  
Ion Channel Regulation ◽  
Channel Regulation ◽  
Scant Attention ◽  
Blood Flow Control ◽  
Hydrolysis Of

The phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP2), has long been established as a major contributor to intracellular signaling, primarily by virtue of its role as a substrate for phospholipase C (PLC). Signaling by Gq-protein–coupled receptors triggers PLC-mediated hydrolysis of PIP2into inositol 1,4,5-trisphosphate and diacylglycerol, which are well known to modulate vascular ion channel activity. Often overlooked, however, is the role PIP2itself plays in this regulation. Although numerous reports have demonstrated that PIP2is critical for ion channel regulation, how it impacts vascular function has received scant attention. In this review, we focus on PIP2as a regulator of ion channels in smooth muscle cells and endothelial cells—the two major classes of vascular cells. We further address the concerted effects of such regulation on vascular function and blood flow control. We close with a consideration of current knowledge regarding disruption of PIP2regulation of vascular ion channels in disease.

scholarly journals Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane

2020 ◽  
Vol 64 (3) ◽  
pp. 513-531 ◽  
Author(s):  
Matilda Katan ◽  
Shamshad Cockcroft
Keyword(s):  
Plasma Membrane ◽  
Ion Channel ◽  
Tyrosine Kinases ◽  
Cell Biology ◽  
Second Messengers ◽  
Membrane Dynamics ◽  
Actin Dynamics ◽  
Ion Channel Regulation ◽  
Channel Regulation ◽  
Phosphoinositide 3 Kinase

Abstract Phosphatidylinositol(4,5) bisphosphate (PI(4,5)P2) has become a major focus in biochemistry, cell biology and physiology owing to its diverse functions at the plasma membrane. As a result, the functions of PI(4,5)P2 can be explored in two separate and distinct roles – as a substrate for phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K) and as a primary messenger, each having unique properties. Thus PI(4,5)P2 makes contributions in both signal transduction and cellular processes including actin cytoskeleton dynamics, membrane dynamics and ion channel regulation. Signalling through plasma membrane G-protein coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and immune receptors all use PI(4,5)P2 as a substrate to make second messengers. Activation of PI3K generates PI(3,4,5)P3 (phosphatidylinositol(3,4,5)trisphosphate), a lipid that recruits a plethora of proteins with pleckstrin homology (PH) domains to the plasma membrane to regulate multiple aspects of cellular function. In contrast, PLC activation results in the hydrolysis of PI(4,5)P2 to generate the second messengers, diacylglycerol (DAG), an activator of protein kinase C and inositol(1,4,5)trisphosphate (IP3/I(1,4,5)P3) which facilitates an increase in intracellular Ca2+. Decreases in PI(4,5)P2 by PLC also impact on functions that are dependent on the intact lipid and therefore endocytosis, actin dynamics and ion channel regulation are subject to control. Spatial organisation of PI(4,5)P2 in nanodomains at the membrane allows for these multiple processes to occur concurrently.

G Protein Regulation of Inwardly Rectifying K+ Channels

Physiology ◽  
1999 ◽  
Vol 14 (5) ◽  
pp. 215-220 ◽  
Author(s):  
Andreas Karschin
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Tyrosine Kinases ◽  
Cellular Responses ◽  
Signaling Cascades ◽  
Channel Activity ◽  
Protein Subunits ◽  
K Channels ◽  
Kir Channel ◽  
Inwardly Rectifying

Inwardly rectifying K+ (Kir) channels respond to receptor-stimulated signaling cascades that involve G proteins and other cytosolic messengers. Channel activity is controlled both by direct coupling of G protein subunits and by phosphorylation via protein serine/threonine and tyrosine kinases. The coincidence of both forms of Kir channel signaling may give rise to complex cellular responses.

scholarly journals Nociceptor Signalling through ion Channel Regulation via GPCRs

2019 ◽  
Vol 20 (10) ◽  
pp. 2488 ◽  
Author(s):  
Isabella Salzer ◽  
Sutirtha Ray ◽  
Klaus Schicker ◽  
Stefan Boehm
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Ion Channel Regulation ◽  
Nociceptive Neurons ◽  
Channel Modulation ◽  
Ion Channel Modulation ◽  
Endogenous Modulators ◽  
G Protein Coupled

The prime task of nociceptors is the transformation of noxious stimuli into action potentials that are propagated along the neurites of nociceptive neurons from the periphery to the spinal cord. This function of nociceptors relies on the coordinated operation of a variety of ion channels. In this review, we summarize how members of nine different families of ion channels expressed in sensory neurons contribute to nociception. Furthermore, data on 35 different types of G protein coupled receptors are presented, activation of which controls the gating of the aforementioned ion channels. These receptors are not only targeted by more than 20 separate endogenous modulators, but can also be affected by pharmacotherapeutic agents. Thereby, this review provides information on how ion channel modulation via G protein coupled receptors in nociceptors can be exploited to provide improved analgesic therapy.

Regulation of NHE3 activity by G protein subunits in renal brush-border membranes

2000 ◽  
Vol 278 (4) ◽  
pp. R1064-R1073 ◽  
Author(s):  
Frederick E. Albrecht ◽  
Jing Xu ◽  
Orson W. Moe ◽  
Ulrich Hopfer ◽  
William F. Simonds ◽  
...  
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Brush Border ◽  
Second Messengers ◽  
Protein Subunit ◽  
Intact Cells ◽  
Protein Subunits ◽  
Brush Border Membranes ◽  
Renal Brush Border Membrane ◽  
Renal Brush Border

NHE3 activity is regulated by phosphorylation/dephosphorylation processes and membrane recycling in intact cells. However, the Na+/H+ exchanger (NHE) can also be regulated by G proteins independent of cytoplasmic second messengers, but the G protein subunits involved in this regulation are not known. Therefore, we studied G protein subunit regulation of NHE3 activity in renal brush-border membrane vesicles (BBMV) in a system devoid of cytoplasmic components and second messengers. Basal NHE3 activity was not regulated by Gsα or Giα, because antibodies to these G proteins by themselves were without effect. The inhibitory effect of D1-like agonists on NHE3 activity was mediated, in part, by Gsα, because it was partially reversed by anti-Gsα antibodies. Moreover, the amount of Gsα that coimmunoprecipitated with NHE3 was increased by fenoldopam in both brush-border membranes and renal proximal tubule cells. Furthermore, guanosine 5′- O-(3-thiotriphosphate) but not guanosine 5′- O-(2-thiodiphosphate), the inactive analog of GDP, increased the amount of Gsα that coimmunoprecipitated with NHE3. The α2-adrenergic agonist, UK-14304 or pertussis toxin (PTX) alone had no effect on NHE3 activity, but UK-14304 and PTX treatment attenuated the D1-like receptor-mediated NHE3 inhibition. The ability of UK-14304 to attenuate the D1-like agonist effect was not due to Giα, because the attenuation was not blocked by anti-Giα antibodies or by PTX. Anti-Gβcommon antibodies, by themselves, slightly inhibited NHE3 activity but had little effect on D1-like receptor-mediated NHE3 inhibition. However, anti-Gβcommon antibodies reversed the effects of UK-14304 and PTX on D1-like agonist-mediated NHE3 inhibition. These studies provide concrete evidence of a direct regulatory role for Gsα, independent of second messengers, in the D1-like-mediated inhibition of NHE3 activity in rat renal BBMV. In addition, β/γ dimers of heterotrimeric G proteins appear to have a stimulatory effect on NHE3 activity in BBMV.

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