nkcc1

Spinal cerebrospinal fluid-contacting neurons (CSF-cNs) form an evolutionary conserved bipolar cells population localized around the central canal of all vertebrates. CSF-cNs were shown to express molecular markers of neuronal immaturity into adulthood, however the impact of their incomplete maturation on the chloride (Cl- ) homeostasis as well as GABAergic signaling remain unknown. Using adult mice from both sexes, in situ hybridization revealed that a proportion of spinal CSF-cNs (18.3%) express the Na+ -K+ -Cl- cotransporter 1 (NKCC1) allowing intracellular Cl- accumulation...

Approximately 22% of Alzheimer's disease (AD) patients suffer from seizures, and the co-occurrence of seizures and epileptiform activity exacerbates AD pathology and related cognitive deficits, suggesting that seizures may be a targetable component of AD progression. Given that alterations in neuronal excitatory:inhibitory (E:I) balance occur in epilepsy, we hypothesized that decreased markers of inhibition relative to those of excitation would be present in AD patients. We similarly hypothesized that in five times familial AD (5XFAD) mice, the E:I imbalance would progress from an early stage (prodromal) to later symptomatic stages, and be further exacerbated by pentylenetetrazol (PTZ) kindling...

Cerebrovascular diseases and their sequalae, such as ischemic stroke, chronic cerebral hypoperfusion, and vascular dementia are significant contributors to adult disability and cognitive impairment in the modern world. Astrocytes are an integral part of the neurovascular unit in the CNS and play a pivotal role in CNS homeostasis, including ionic and pH balance, neurotransmission, cerebral blood flow, and metabolism. Astrocytes respond to cerebral insults, inflammation, and diseases through unique molecular, morphological, and functional changes, collectively known as reactive astrogliosis...

Neuroinflammation contributes to the pathophysiology of major depressive disorder (MDD) by inducing neuronal excitability via dysregulation of microglial brain-derived neurotrophic factor (BDNF), Na-K-Cl cotransporter-1 (NKCC1), and K-Cl cotransporter-2 (KCC2) due to activation of BDNF-tropomyosin receptor kinase B (TrkB) signaling. Allosteric modulation of α7 nAChRs has not been investigated on BDNF, KCC2, and NKCC1 during LPS-induced depressive-like behavior. Therefore, we examined the effects of PNU120596, an α7 nAChR positive allosteric modulator, on the expression of BDNF, KCC2, and NKCC1 in the hippocampus and prefrontal cortex using Western blot analysis, immunofluorescence assay, and real-time polymerase chain reaction...

Autism spectrum disorder (ASD) is thought to result from susceptibility genotypes and environmental risk factors. The offspring of women who experience pregnancy infection have an increased risk for autism. Maternal immune activation (MIA) in pregnant animals produces offspring with autistic behaviors, making MIA a useful model for autism. However, how MIA causes autistic behaviors in offspring is not fully understood. Here, we show that NKCC1 is critical for mediating autistic behaviors in MIA offspring. We confirmed that MIA induced by poly(I:C) infection during pregnancy leads to autistic behaviors in offspring...

Aquaporin-5 (AQP5) water channel, transmembrane protein 16A (TMEM16A) Ca2+ -activated Cl- channel, and Na+ -K+ -2Cl- cotransporter (NKCC1) are membrane proteins on salivary gland acinar cells that function in watery saliva secretion. We examined their expression changes in rat parotid glands under reduced mastication. Rats were either fed regular chow as a control group, fasted for 48 hr or fed a liquid diet for 48 hr or 1 week to reduce mastication. The parotid glands were then resected to analyze the protein and mRNA levels by immunofluorescence, immunoblotting, and reverse-transcription quantitative PCR (RT-qPCR)...

Pictured, described, speculated upon, for close to 400 years, the function of the rectal gland of elasmobranchs remained unknown. In the late 1950s Burger discovered that the rectal gland of Squalus acanthias secreted an almost pure solution of sodium chloride, isosmotic with blood, that could be stimulated by volume expansion of the fish. Twenty five years later, Stoff discovered that the secretion of the gland was mediated by adenyl cyclase. Studies since then have shown that Vasoactive intestinal peptide (VIP) is the neurotransmitter responsible for activating adenyl cyclase; however, the amount of circulating VIP does not change in response to volume expansion...

BACKGROUND: Astrogliosis and white matter lesions (WML) are key characteristics of vascular contributions to cognitive impairment and dementia (VCID). However, the molecular mechanisms underlying VCID remain poorly understood. Stimulation of Na-K-Cl cotransport 1 (NKCC1) and its upstream kinases WNK (with no lysine) and SPAK (the STE20/SPS1-related proline/alanine-rich kinase) play a role in astrocytic intracellular Na+ overload, hypertrophy, and swelling. Therefore, in this study, we assessed the effect of SPAK inhibitor ZT-1a on pathogenesis and cognitive function in a mouse model of VCID induced by bilateral carotid artery stenosis (BCAS)...

Calcium signaling in vascular endothelial cells (ECs) and smooth muscle cells (VSMC) is essential for the regulation of vascular tone. However, the changes to intracellular Ca2+ concentrations are often influenced by sex differences. Furthermore, a large body of evidence shows that sex hormone imbalance leads to dysregulation of Ca2+ signaling and this is a key factor in the pathogenesis of cardiovascular diseases. In this review, the effects of estrogens and androgens on vascular calcium-handling proteins are discussed, with emphasis on the associated genomic or non-genomic molecular mechanisms...

Synaptic transmission mediated by GABAA receptors (GABAARs) in adult, principal striatal spiny projection neurons (SPNs) can suppress ongoing spiking, but its effect on synaptic integration at subthreshold membrane potentials is less well characterized, particularly those near the resting down-state. To fill this gap, a combination of molecular, optogenetic, optical, and electrophysiological approaches were used to study SPNs in mouse ex vivo brain slices, and computational tools were used to model somatodendritic synaptic integration...

BACKGROUND: Acting on the main target of dopaminergic cells, the striatal γ-aminobutyric acid (GABA)-ergic cells, might be a new way to treat persons with Parkinson's disease (PD). OBJECTIVE: The objective of this study was to assess the efficacy of bumetanide, an Na-K-Cl cotransporter (NKCC1) inhibitor, to improve motor symptoms in PD. METHODS: This was a 4-month double-blind, randomized, parallel-group, placebo-controlled trial of 1...

In physiological conditions, the intracellular chloride concentration is much lower than the extracellular. As GABAA channels are permeable to anions, the reversal potential of GABAA is very close to that of Cl- , which is the most abundant free anion in the intra- and extracellular spaces. Intracellular chloride is regulated by the activity ratio of NKCC1 and KCC2, two chloride-cation cotransporters that import and export Cl- , respectively. Due to the closeness between GABAA reversal potential and the value of the resting membrane potential in most neurons, small changes in intracellular chloride have a major functional impact, which makes GABAA a uniquely flexible signaling system...

The solute carrier family 12 ( SLC12 ) of cation-chloride cotransporters (CCCs) comprises potassium chloride cotransporters (KCCs, e.g. KCC1, KCC2, KCC3, and KCC4)-mediated Cl- extrusion, and sodium potassium chloride cotransporters (N[K]CCs, NKCC1, NKCC2, and NCC)-mediated Cl- loading. The CCCs play vital roles in cell volume regulation and ion homeostasis. Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues. In recent years, there have been considerable advances in our understanding of CCCs' control mechanisms in cell volume regulations, with many techniques developed in studying the functions and activities of CCCs...

BACKGROUND: Reperfusion therapy after ischemic cerebral stroke may cause cerebral ischemia-reperfusion injury (CIRI), and cerebral edema is an important factor that may aggravate CIRI. Our study aimed to dynamically monitor the development of early cytotoxic edema after CIRI by magnetic resonance imaging (MRI) and to validate it using multiple histological imaging methods. METHODS: Male Sprague Dawley rats were divided into sham and CIRI groups. T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)-MRI scans were performed in the sham and CIRI groups after reperfusion...

Increased expression of the angiotensin II AT1A receptor (encoded by Agtr1a) and Na+ -K+ -Cl- cotransporter-1 (NKCC1, encoded by Slc12a2) in the hypothalamic paraventricular nucleus (PVN) contributes to the development of hypertension. However, little is known about transcriptional control of Agtr1a and Slc12a2 in the PVN in hypertension. DNA methylation is a critical epigenetic mechanism that regulates gene expression. Here, we determined whether transcriptional activation of Agtr1a and Slc12a2 results from altered DNA methylation in spontaneously hypertensive rats (SHR)...

The sodium, potassium, and chloride cotransporter 1 (NKCC1) plays a key role in tightly regulating ion shuttling across cell membranes. Lately, its aberrant expression and function have been linked to numerous neurological disorders and cancers, making it a novel and highly promising pharmacological target for therapeutic interventions. A better understanding of how NKCC1 dynamically operates would therefore have broad implications for ongoing efforts toward its exploitation as a therapeutic target through its modulation...

The Kir4.1 channel, an inwardly rectifying potassium ion (K+ ) channel, is located in the hair cells of the organ of Corti as well as the intermediate cells of the stria vascularis. The Kir4.1 channel has a crucial role in the generation of endolymphatic potential and maintenance of the resting membrane potential. However, the role and functions of the Kir4.1 channel in the progenitor remain undescribed. To observe the role of Kir4.1 in the progenitor treated with the one-shot ototoxic drugs (kanamycin and furosemide), we set the proper condition in culturing Immortomouse-derived HEI-OC1 cells to express the potassium-related channels well...

OBJECTIVE: Right dorsal colitis causes chronic colic associated with long-term treatment with nonsteroidal antiinflammatory drugs (NSAIDs). This study was designed to determine if NSAIDs could inhibit anion transporters that protect against intestinal mucosal injury in other species. ANIMALS: 20 healthy horses. METHODS: The effects of indomethacin (INDO) and firocoxib (FIR), on short-circuit current (Isc) in mucosa from the right dorsal colon (RDC) and right ventral colon (RVC) were measured in Ussing chambers by standard electrophysiological techniques...

Neuroinflammation is a pathological event associated with many neurological disorders, including dementia and stroke. The choroid plexus (ChP) is a key structure in the ventricles of the brain that secretes cerebrospinal fluid (CSF), forms a blood-CSF barrier, and responds to disease conditions by recruiting immune cells and maintaining an immune microenvironment in the brain. Despite these critical roles, the exact structural and functional changes to the ChP over post-stroke time remain to be elucidated. We induced ischemic stroke in C57BL/6J mice via transient middle cerebral artery occlusion which led to reduction of cerebral blood flow and infarct stroke...

People with primary focal hyperhidrosis (PFH) usually have an overactive sympathetic nervous system, which can activate the sweat glands through the chemical messenger of acetylcholine. The role of aquaporin 5 (AQP5) and Na-K-2Cl co-transporter 1 (NKCC1) in PFH is still unknown. The relative mRNA and protein levels of AQP5 and NKCC1 in the sweat gland tissues of three subtypes of PFH patients (primary palmar hyperhidrosis, PPH; primary axillary hyperhidrosis, PAH; primary craniofacial hyperhidrosis, PCH) were detected with Real-Time PCR (qPCR) and Western blot...