nkcc1

We report that half striatal cholinergic interneurons are dual transmitter cholinergic and GABAergic interneurons (CGINs) expressing ChAT, GAD65, Lhx7, and Lhx6 mRNAs, labeled with GAD and VGAT, generating monosynaptic dual cholinergic/GABAergic currents and an inhibitory pause response. Dopamine deprivation increases CGINs ongoing activity and abolishes GABAergic inhibition including the cortico-striatal pause because of high [Cl- ]i levels. Dopamine deprivation also dramatically increases CGINs dendritic arbors and monosynaptic interconnections probability, suggesting the formation of a dense CGINs network...

Smolting Atlantic salmon exhibit a seasonal increase in seawater tolerance that is associated with changes in the abundance of major gill ion-transporter transcripts and proteins. In the present study, we investigate how the transcript and protein abundance of specific ion-transporter isoforms relate to each other during smolt development and seawater acclimation, and how each correlates to seawater tolerance. We show that during smolt development both mRNA and protein abundance of gill Na+ /K+ -ATPase α1a subunit (NKAα1a) decreased but the decrease in the mRNA was five-times greater than that of the protein...

Serotonergic neurons in the dorsal raphe nucleus (DRN) act as wake-inducing neurons in the sleep-wake cycle and are controlled by gamma-aminobutyric acid (GABA) synaptic inputs. We investigated daily changes in GABAergic inhibition of the rat DRN neurons and the role of nitric oxide (NO) and cation-chloride co-transporters in the GABAergic action. Neuronal NO synthase (nNOS) was co-expressed in 74% of serotonergic DRN neurons and nNOS expression was higher during daytime (the sleep cycle) than that during nighttime (the wake cycle)...

Worldwide, 500,000 cases of head and neck cancer (HNC) are reported each year and the primary treatment for HNC is radiotherapy. Although the goal of radiotherapy is to target the tumor, secondary exposure occurs in surrounding normal tissues, such as the salivary glands. As a result, despite successful treatment of the cancer, patients are left with long-term side effects due to direct damage to the salivary glands. The effect is chronic and currently there is no treatment. Stem cells are an attractive therapeutic option for treatment of radiation-induced glandular dysfunction because of the potential to regenerate damaged cell populations and restore salivary gland function...

Cerebral white matter is vulnerable to ischemic condition. However, no effective treatment to alleviate or restore the myelin damage caused by chronic cerebral hypoperfusion has been found. Na+ -K+ -Cl- cotransporter 1 (NKCC1), a Na+ -K+ -Cl- cotransporter widely expressed in the central nervous system (CNS), involves in regulation of cell swelling, EAA release, cell apoptosis, and proliferation. Nevertheless, the role of NKCC1 in chronic hypoperfusion-induced white matter lesions (WMLs) has not been explored...

We recently showed that constraining eye contact leads to exaggerated increase of amygdala activation in autism. Here, in a proof of concept pilot study, we demonstrate that administration of bumetanide (a NKCC1 chloride importer antagonist that restores GABAergic inhibition) normalizes the level of amygdala activation during constrained eye contact with dynamic emotional face stimuli in autism. In addition, eye-tracking data reveal that bumetanide administration increases the time spent in spontaneous eye gaze during in a free-viewing mode of the same face stimuli...

Specific pharmacological blockade of KCNQ (Kv7) channels with XE991 rapidly (within 20 min) and profoundly alters inner ear gravity receptor responses to head motion (Lee et al., 2017). We hypothesized that these effects were attributable to the suppression of K+ secretion following blockade of KCNQ1-KCNE1 channels in vestibular dark cells and marginal cells. To test this hypothesis, K+ secretion was independently inhibited by blocking the Na+ -K+ -2Cl- cotransporter (NKCC1, Slc12a2) rather than KCNQ1-KCNE1 channels...

Quantitative phase imaging (QPI) has recently emerged as a powerful new quantitative microscopy technique suitable for the noninvasive exploration of the structure and dynamics of transparent specimens, including living cells in culture. Indeed, the quantitative phase signal (QPS), induced by transparent living cells, can be detected with a nanometric axial sensitivity, and contains a wealth of information about both cell morphology and content. However, QPS is also sensitive to various sources of experimental noise...

Interstitial fluid pressure (IFP) presents a barrier to drug uptake in solid tumors, including the aggressive primary brain tumor glioblastoma multiforme (GBM). It remains unclear how fluid dynamics impacts tumor progression and can be targeted therapeutically. To address this issue, a novel telemetry-based approach was developed to measure changes in IFP during progression of GBM xenografts. Antisecretory factor (AF) is an endogenous protein that displays anti-secretory effects in animals and patients. Here, endogenous induction of AF protein or exogenous administration of AF peptide reduced IFP and increased drug uptake in GBM xenografts...

Spinal cord injury (SCI) affects more than 2.5 million people worldwide. Spinal cord edema plays critical roles in the pathological progression of SCI. This study aimed to delineate the roles of aquaporin 4 (AQP4) and Na+-K+-Cl- cotransporter 1 (NKCC1) in acute phase edema and tissue destruction after SCI and to explore whether inhibiting both AQP4 and NKCC1 could improve SCI-induced spinal edema and damage. Rat SCI model was established by modified Allen's method. Spinal cord water content, cerebrospinal fluid lactose dehydrogenase (LDH) activity, AQP4 and NKCC1 expression, and spinal cord pathology from 30 min to 7 days after SCI were monitored...

Huntington's disease (HD) is classically characterized as a movement disorder, however cognitive impairments precede the motor symptoms by ∼15 y. Based on proteomic and bioinformatic data linking the Huntingtin protein (Htt) and KCC2, which is required for hyperpolarizing GABAergic inhibition, and the important role of inhibition in learning and memory, we hypothesized that aberrant KCC2 function contributes to the hippocampal-associated learning and memory deficits in HD. We discovered that Htt and KCC2 interact in the hippocampi of wild-type and R6/2-HD mice, with a decrease in KCC2 expression in the hippocampus of R6/2 and YAC128 mice...

It is well known that the electrical signaling in neuronal networks is modulated by chloride (Cl- ) fluxes via the inhibitory GABAA and glycine receptors. Here, we discuss the putative contribution of Cl- fluxes and intracellular Cl- to other forms of information transfer in the CNS, namely the bidirectional communication between neurons and astrocytes. The manuscript (i) summarizes the generic functions of Cl- in cellular physiology, (ii) recaps molecular identities and properties of Cl- transporters and channels in neurons and astrocytes, and (iii) analyzes emerging studies implicating Cl- in the modulation of neuroglial communication...

Autism spectrum disorder (ASD) and temporal lobe epilepsy exhibit remarkable comorbidity, but for reasons not clearly understood. To reveal a common pathophysiological mechanism, we here describe and characterize an in vitro epileptiform activity in the rat hippocampus that exhibits common features with in vivo activity in rodent ASD models. We discovered the development of this activity in the CA1 region of horizontal slices after prolonged interictal-like epileptiform activity in the CA3 region that was provoked by incubation in high potassium artificial cerebrospinal fluid...

Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP), which may aggravate hyperglycemia and nephropathy. However, the mechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in supraoptic nucleus (SON) slices from streptozotocin (STZ)-induced DM rats and vehicle-treated control rats revealed that γ-aminobutyric acid (GABA) functions generally as an excitatory neurotransmitter in the AVP neurons of STZ rats, whereas it usually evokes inhibitory responses in the cells of control animals...

We develop a mathematical model of a salivary gland acinar cell with the objective of investigating the role of two [Formula: see text] exchangers from the solute carrier family 4 (Slc4), Ae2 (Slc4a2) and Ae4 (Slc4a9), in fluid secretion. Water transport in this type of cell is predominantly driven by [Formula: see text] movement. Here, a basolateral [Formula: see text] adenosine triphosphatase pump (NaK-ATPase) and a [Formula: see text]-[Formula: see text]-[Formula: see text] cotransporter (Nkcc1) are primarily responsible for concentrating the intracellular space with [Formula: see text] well above its equilibrium potential...

Na+ :K+ :2Cl- cotransporters (NKCCs) belong to the SLC12A family of cation-coupled Cl- transporters. We investigated whether enamel-producing mouse ameloblasts express NKCCs. Transcripts for Nkcc1 were identified in the mouse dental epithelium by RT-qPCR and NKCC1 protein was immunolocalized in outer enamel epithelium and in the papillary layer but not the ameloblast layer. In incisors of Nkcc1 -null mice late maturation ameloblasts were disorganized, shorter and the mineral density of the enamel was reduced by 10% compared to wild-type controls...

OBJECTIVE: The phenotype of the cells present in the ductal region of salivary glands have been well characterized. However, it is imperative to identify novel biomarkers that can identify different cell types present in other glandular components for the development of therapeutic strategies and diagnostics of salivary gland disorders and malignancies. Our study aimed at the characterization of the expression and distribution of various cell surface markers, especially with a focus on CD29 in human fetal as well as adult glands...

BACKGROUND: Salivary gland (SG) injurious agents are all translated into loss of salivation (xerostomia). An association has been established between activation of innate immunity and SG injury and dysfunction. However, it remains unclear how the secretory epithelia respond by halting saliva production. METHODS: C57BL/6 submandibular glands (SMGs) were acutely challenged using a single dose of the innate immune stimulant: polyinosinic-polycytidylic acid (poly (I:C))...

Individuals with 22q11.2 microdeletion syndrome (22q11.2 DS) show cognitive and behavioral dysfunctions, developmental delays in childhood and risk of developing schizophrenia and autism. Despite extensive previous studies in adult animal models, a possible embryonic root of this syndrome has not been determined. Here, in neurons from a 22q11.2 DS mouse model (Lgdel+/- ), we found embryonic-premature alterations in the neuronal chloride cotransporters indicated by dysregulated NKCC1 and KCC2 protein expression levels...

Identification of the causal effects of specific proteins on recurrent and partially reversible hearing loss has been difficult because of the lack of an animal model that provides reversible gene knockdown. We have developed the transgenic mouse line Actin-tTS::Nkcc1tetO/tetO for manipulatable expression of the cochlear K+ circulation protein, NKCC1. Nkcc1 transcription was blocked by the binding of a tetracycline-dependent transcriptional silencer to the tetracycline operator sequences inserted upstream of the Nkcc1 translation initiation site...