A Short Note On Na K Cl Cotransporter

-If the potassium transport pump was blocked the leakage channels would still be open allowing Na+ to

​Cystic fibrosis is an inherited, chronic disease of the secretory glands which directly affects the lungs and digestive system (NLM, 2015). To look more closely at a cellular level, there is a defective gene in which their protein product that regulates movement of sodium

Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductor regulator (CFTR) gene, which codes for the CFTR protein (Sartin, 2013). The CFTR protein is a chloride channel present in secretory glands and the epithelial cells of numerous organs. Due to the high affinity of chloride, sodium and water, CFTR protein plays a vital role in the homeostatic

Cystic fibrosis (CF), is an autosomal recessive disorder [figure 1.], caused by a mutation in two genes on chromosome 7 – the genes responsible for the way water and salts pass in and out of the cells in the body. CF affects the secretion and reabsorption of chloride ions, producing a much thicker than normal layer of mucus (in the lungs, pancreas and liver primarily) that is ideal for bacteria and infection to flourish. The faulty gene may fail to produce the cystic fibrosis transmembrane conductance regulator (CFTR) protein or may produce the protein however this protein is faulty is such a way that it does not regulate chloride secretion and reabsorption properly or at all. Currently there are a wide array of

Cystic Fibrosis is the result of a genetic mutation in the CFTR gene on chromosome 7. This disease is more common to the Northern European population, with over 1500 different mutations that can occur on this gene. The most common is a deletion of phenylalanine at position 508 (ΔF508) [2] - this occurs in 66% of cystic fibrosis patients [1]. The cystic fibrosis transmembrane conductance regulator (CFTR) protein is an ATP gated chlorine ion channel found in epithelial cells at the apical surfaces. It belongs to the ATP-binding cassette (ABC) membrane transporter superfamily[4] and contains two membrane spanning domains, consisting of six transmembrane α-helices, and two nuclear binding domains (NBD) whose activity are regulated by the R (regulatory) domain (fig.1).

Cystic fibrosis (CF) is a progressive condition in which epithelial exocrine glands are obstructed (Howe, 2001). Whilst many organs and bodily systems are disrupted by CF, the lungs and gastrointestinal organs are predominantly affected; it is also most common amongst the Caucasian population due to the autosomal recessive gene (Quitter et al., 2003 cited in Wolfe & Mash, 2006, pg 514). The faulty gene effects the production of cystic fibrosis transmembrane conductance regulator protein, which is responsible for the formation of molecular tunnels which monitor the movement of salts and water from the cells (Hopkin, 2010 pg 4).

The protein of the cystic fibrosis gene is called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The gene is located on 7q31.2 long arm of chromosome 7 at position 31.2. The CF gene also has 27 exons and is made up of 250,000 DNA nucleotides. CFTR moves chloride ions out of cells which is very important for salt and water balances on the epithelial cells.

Na+ , K+ and Cl- cotransporter is envolved in electroneutral transport at apical surface, which is driven by low concentration of these ions. This low concentration of ions is achieved by basolateral Na+ and K+ contertransporter (sodium-potassium adenosine triphosphatase) and basolateral chloride ion channel by facilitated diffusion (CLC-kb). Potassium ion is capable of diffusing back to lumen through apical potassium channel (ROMK) and returns net positive charge to lumen, this is important for reabsorption of calcium and magnesium

It is responsible for carrying Na+ to activate action potentials. The sodium channel is affected and causes membrane depolarization and weakness. The voltage of the sodium channels slows down significantly and results in low serum K+ levels. With low serum K+

Notably, in congruent with our finding, NAC has been shown to provide cysteine to cells even in the absence of cysteine transport [47, 48]. Interestingly, the present finding also suggests a possibility that oxidative stress can regulate EAAC1 since NAC prevented the E-induced EAAC1 loss (Fig 7C). In support of this finding, under stressful conditions, such as oxidative and chemical stress, regulation and/or alteration of EAAC1 are evident at the level of expression, activity, and its membrane trafficking [49-52]. Clinically, NAC is the widely used Cys prodrug due to its safety, tolerability, and its ability to undergo rapid hydrolysis to deliver Cys immediately following cellular entry [46, 53, 54].

The first pathway transports proteins between the cytosol and the nucleus by way of nuclear pore complexes in the nuclear envelope. With protein translocation, the protein directly transports to an exact protein across the membrane. Vesicular transport is where the spherical transport vesicle becomes loaded with cargo within the lumen. An example of this pathway, soluble proteins from the ER to the Golgi apparatus by way of transport vesicles. The pathways require energy this can be supplied by ATP hydrolysis. Chaperone proteins facilitate in passing proteins to other

CLDN19 mice developed features of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis, which contain hypomagnesemia, hypercalciuria and hypermagnesuria. Knockdown CLDN19 expression by siRNA causes the loss claudin-16 from TJs in TAL, however, knockdown CLDN16 by siRNA produce the result similar to claudin-19. Both Claudin-16 and claudin-19 shows normal barrier function after run out of TJs but it is the abnormal ion selectivity. These data indicated that heteromeric claudin-16 claudin-19 react with each other are necessary to produce TJ structure and a paracellular pathway of cation selective. Besides, some mutations of CLDN16 and CLDN19 avoid this interaction, which means the function of TAL for claudins interaction in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis.

The serum sodium levels appear to be higher than normal because the water is shifting from the ECF into the intracellular compartments (ICF).

Effective transport systems in multicellular plants and animals, although with apparent differences, have similarities as they all possess a system of vessels in which substances are transported, a driving mechanism to ensure that substances move in the correct direction and importantly, a suitable transport medium.

transporters vary between eukaryote and prokaryote organisms, ABC protein shows highly conservative amino acid domains within NBDs. However, NBD have three well studies motifs; ATP-binding sequences for the phosphate-binding loop (P-loop or Walker A motif), walker B boxes, and ABC signature, ex (LIVMYA), which is fix in between Walker boxes (Akifumi Sugiyama, et al, 2006)