Structural determinants and significance of regulation of electrogenic Na+-HCO 3 − cotransporter stoichiometry

2002 ◽  
Vol 283 (5) ◽  
pp. F876-F887 ◽  
Author(s):  
Eitan Gross ◽  
Ira Kurtz
Keyword(s):  
Molecular Mechanisms ◽  
Mutational Analysis ◽  
Ph Regulation ◽  
Reversal Potential ◽  
Cell Type ◽  
Coupling Ratio ◽  
Structural Determinants ◽  
Intracellular Ph Regulation ◽  
Important Functional Property ◽  
Dependent Signaling Pathway

Na+-HCO[Formula: see text]cotransporters play an important role in intracellular pH regulation and transepithelial HCO[Formula: see text] transport in various tissues. Of the characterized members of the HCO[Formula: see text]transporter superfamily, NBC1 and NBC4 proteins are known to be electrogenic. An important functional property of electrogenic Na+-HCO[Formula: see text] cotransporters is their HCO[Formula: see text]:Na+ coupling ratio, which sets the transporter reversal potential and determines the direction of Na+-HCO[Formula: see text] flux. Recent studies have shown that the HCO[Formula: see text]:Na+ transport stoichiometry of NBC1 proteins is either 2:1 or 3:1 depending on the cell type in which the transporters are expressed, indicating that the HCO[Formula: see text]:Na+ coupling ratio can be regulated. Mutational analysis has been very helpful in revealing the molecular mechanisms and signaling pathways that modulate the coupling ratio. These studies have demonstrated that PKA-dependent phosphorylation of the COOH terminus of NBC1 proteins alters the transport stoichiometry. This cAMP-dependent signaling pathway provides HCO[Formula: see text]-transporting epithelia with an efficient mechanism for modulating the direction of Na+-HCO[Formula: see text] flux through the cotransporter.

Mechanisms of intracellular pH regulation during postischemic reperfusion of diabetic rat hearts

Diabetes ◽  
1995 ◽  
Vol 44 (2) ◽  
pp. 196-202 ◽  
Author(s):  
N. Khandoudi ◽  
M. Bernard ◽  
P. Cozzone ◽  
D. Feuvray
Keyword(s):  
Intracellular Ph ◽  
Ph Regulation ◽  
Diabetic Rat ◽  
Intracellular Ph Regulation ◽  
Postischemic Reperfusion ◽  
Rat Hearts

scholarly journals Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens

2021 ◽  
Author(s):  
Hee-Dae Kim ◽  
Jing Wei ◽  
Tanessa Call ◽  
Nicole Teru Quintus ◽  
Alexander J. Summers ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Current Treatment ◽  
Specific Cell ◽  
Excitatory Synapses ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Circuit Function

AbstractDepression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

A novel epithelial cell from neonatal rat lung: isolation and differentiated phenotype

1990 ◽  
Vol 259 (6) ◽  
pp. L415-L425 ◽  
Author(s):  
P. E. Roberts ◽  
D. M. Phillips ◽  
J. P. Mather
Keyword(s):  
Epithelial Cell ◽  
Molecular Mechanisms ◽  
Basal Medium ◽  
Fold Increase ◽  
Cell Types ◽  
Cell Number ◽  
Neonatal Rat ◽  
Rat Lung ◽  
Cell Type

A novel epithelial cell from normal neonatal rat lung has been isolated, established, and maintained for multiple passages in the absence of serum, without undergoing crisis or senescence. By careful manipulation of the nutrition/hormonal microenvironment, we have been able to select, from a heterogeneous population, a single epithelial cell type that can maintain highly differentiated features in vitro. This cell type has characteristics of bronchiolar epithelial cells. A clonal line, RL-65, has been selected and observed for greater than 2 yr in continuous culture. It has been characterized by ultrastructural, morphological, and biochemical criteria. The basal medium for this cell line is Ham's F12/Dulbecco's modified Eagle's (DME) medium plus insulin (1 micrograms/ml), human transferrin (10 micrograms/ml), ethanolamine (10(-4) M), phosphoethanolamine (10(-4) M), selenium (2.5 x 10(-8) M), hydrocortisone (2.5 x 10(-7) M), and forskolin (5 microM). The addition of 150 micrograms/ml of bovine pituitary extract to the defined basal medium stimulates a greater than 10-fold increase in cell number and a 50- to 100-fold increase in thymidine incorporation. The addition of retinoic acid results in further enhancement of cell growth and complete inhibition of keratinization. We have demonstrated a strategy that may be applicable to isolating other cell types from the lung and maintaining their differentiated characteristics for long-term culture in vitro. Such a culture system promises to be a useful model in which to study cellular events associated with differentiation and proliferation in the lung and to better understand the molecular mechanisms involved in these events.

scholarly journals Cell type influences the molecular mechanisms involved in hormonal regulation of ERG K+ channels

2012 ◽  
Vol 463 (5) ◽  
pp. 685-702 ◽  
Author(s):  
Luis Carretero ◽  
Francisco Barros ◽  
Pablo Miranda ◽  
Jorge Fernández-Trillo ◽  
Angeles Machín ◽  
...  
Keyword(s):  
Hormonal Regulation ◽  
Molecular Mechanisms ◽  
Cell Type ◽  
K Channels
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