What is the difference between channels and transporters

The different mean open times MOT during each set of records are indicative of modal gating and result in activations of different durations and ensemble averages that decay with different time-courses. Image from the Howe Lab. Your browser is antiquated and no longer supported on this website. Please update your browser or switch to Chrome, Firefox or Safari. So, it can be observed unceasing traffic in the plasma membrane. Molecules and ions are moving across a membrane based on diffusion principal particle movement from the region of higher concentration to a region of lower concentration which is known as passive transportation.

But in some instances, the molecules and ions are moved against their concentration gradient which is known as active transportation that is spontaneously supported by ATP.

The lipid bilayers are impermeable to most of the molecules and ions except for water, O 2, and CO 2 and it is the major constraint encounters in the transportation of molecules and ions across a biological membrane. So, the active transportation and passive transportation of molecules and ions across membranes are extremely important for living cells.

The key difference between ions channel and transporter can be explained as ion channels are involved in the passive transportation of ions.

On the contrary, transporters are involved in the active transportation of ions by consuming ATP. Overview and Key Difference 2. What is Ion Channel 3. What is Ion Transporter 4.

Similarities Between Ion Channel and Transporter 5. The ion channel receptors are multimeric proteins resting and located on the plasma membrane. Each of these proteins is arranged in such a way they form pore extending passageway from one side of the membrane to another.

These passageways are called as ion channels. Ion channels possess the ability to open and close according to chemical, electrical and mechanical signals which they receive from cell outside. The ion channel opening is a fleeting event.

This takes only a few milliseconds. Pumps utilise a source of energy e. Channels, on the other hand, provide a pore through the membranes that allows ions or molecules to diffuse downhill in energy. The pore is not permanently in an open state but instead undergoes conformational transitions between open and closed states, with the open probability usually dependent on either membrane voltage voltage-gated channels or the presence of another molecule ligand-gated channels.

Transporters, like pumps, transport ions or molecules across a membrane in a direction that is uphill in energy and therefore require a source of energy. However, in contrast to pumps, the energy does not come directly from the sun or a chemical reaction, but rather from the coupling of the transport to the diffusion of an ion downhill in energy.

This process is called secondary active transport, whereas pump activity is termed primary active transport. Channel activity, on the other hand, is referred to as facilitated diffusion. ATP drives the sodium pump. Email: catherine. Email: Mary. This is a Responsive Web Design Site to provide an optimal viewing experience, easy reading and navigation across a wide range of devices from desktop computers to laptops, tablets and smart phones.

Not supported are IE9 and below. To offer your services as a book or software reviewer for Chemistry in Australia , please contact Damien Blackwell at damo34 internode. Access features, news and views from the latest issue and from our chemistry archives. June Pumps, channels and transporters: how chemists can help. Energetics of transport proteins. The different mechanisms of pumps and channels. Crystal structure of calcium ATPase with two bound calcium ions.

Although previously the blindness was believed to be the result of osteopetrotic narrowing of the optic nerve canal Steward, , retinal degeneration is a direct effect of disruption of ClC-7 or Ostm1 at retinal neurons Kasper et al. Neurodegeneration is the probable cause of death of ClC-7 KO mice at approximately 6 weeks. They present neuronal cell loss, particularly in the hippocampus and cerebral cortex, as well as lysosomal storage material scattered throughout the neuronal somata Kasper et al.

Neurodegeneration and lysosomal storage disease are cell-autonomous effects of disruption of ClC-7 as demonstrated by tissue-specific ClC-7 KO mice.

In this study, PTCs and neurons lacking or expressing ClC-7 were compared within the same environment; only cells devoid of ClC-7 displayed lysosomal disease Wartosch et al. These intriguing results concerning the function of ClC-7 in lysosomes led to the generation of two other ClC-7 mice models, the ClC-7 unc mice Weinert et al. However, although ClC-7 unc mice presented neuronal cell loss and lysosomal storage disease similar to the ClC-KO mice, the osteopetrotic phenotype was partially rescued by the presence of pure Cl - currents Weinert et al.

Meanwhile, ClC-7 td mice displayed similar osteopetrotic phenotype to ClC-7 KO mice, but a delayed and less severe neurodegeneration Weinert et al. Taken together, these results suggest that the physical presence of the non-functioning ClC-7 td alone was sufficient to rescue the normal fur pigmentation and alleviate neurodegeneration, whereas ClC-7 unc Cl - currents had a positive effect in partially rescued osteopetrosis and normal fur pigmentation, but a negative effect in neurodegeneration Weinert et al.

The precise role of ClC-7 in lysosomes is still obscure, as is the previously discussed role of ClC-5 in endosomes. The last sections of this review focuses on ClC-3, -4, and -6, which have uncertain physiological functions.

Although mutations or dysfunction of these ClCs have not been linked directly to specific human diseases, mouse models have demonstrated important phenotypes that are worth discussing here. ClC-3 is a broadly expressed intracellular ClC protein with controversial biophysical and physiological characteristics. Several mutually conflicting Cl - currents have been attributed to ClC ClC-3 presents very low cell surface expression, even when heterologously overexpressed, which has hindered a thorough analysis of its biophysical properties.

Nevertheless, in some studies, small but strongly outwardly rectifying Cl - currents were found Li et al. ClC-3 is expressed in most tissues, including the brain, retina, adrenal gland, pancreas, intestines, epididymis, kidney, liver, skeletal muscle, and heart Kawasaki et al.

It mainly resides in endosomes, where it was found co-localized with ClC-4 and ClC-5, and also with both early and late endosomal markers Figure 5 Suzuki et al. CLC-3 is also found in synaptic vesicles Stobrawa et al. Three different ClC-3 KO mouse lines displayed similar phenotypes of severe degeneration of the retina and brain, with prominent effects in the hippocampus Stobrawa et al.

In one model, signs of lysosomal storage disease were observed Yoshikawa et al. The mechanism by which ClC-3 causes neurodegeneration is still unclear. Although ClC-3 was thought to provide the electrical shunt for acidification of intracellular compartments like the other ClC exchangers, its role in endosomes and synaptic vesicles is still controversial.

Synaptic vesicles from ClC-3 KO mice exhibit reduced glutamate uptake, but this feature has been ascribed to diminished levels of the vesicular glutamate transporter VGLUT1 Stobrawa et al. The authors observed enlargement of synaptic vesicles and increased glutamate content in cells lacking ClC The probability of vesicle fusion and release of its content was also increased in those cells, indicating that exaggerated release of glutamate in the synaptic cleft contributes to neurodegeneration in ClC-3 KO mice Guzman et al.

Lack of ClC-3 provoked apoptosis of intestinal epithelial cells, causing disruption of the epithelial barrier and bacterial invasion. In an ApoE null mice background, further disruption of ClC-3 reduced the size of atherosclerotic lesions present in the aorta. This inhibition was attributed to suppressed levels of reactive oxygen species and NADPH oxidase activity—direct effects of angiotensin-II—that are suppressed by ClC-3 disruption Liu et al.

Three different splicing variants of ClC-3 ClC-3a, ClC-3b, and ClC-3c were described in the brain with different subcellular localization but similar transport function Guzman et al. Another splicing variant, ClC-3d, was described in mouse livers as displaying different localizations but identical transport properties Okada et al.

The number of splicing variants with different subcellular localizations might explain the diversity of functions ascribed to ClC-3; the study of these isoforms could be a promising direction for further study of the precise function and localization of ClC-3 proteins, which could provide an explanation for the phenotypes described in KO mice.

ClC-4 is a broadly expressed ClC exchanger found in various tissues which differ between species. It is found mostly in the muscles, brain, and heart of humans van Slegtenhorst et al. Interestingly, the gene encoding ClC-4 is localized on chromosome 7 in inbred laboratory mice, but in humans and rats, the gene resides on the X chromosome Rugarli et al. This may partially explain the variety and species-specificity of expression patterns.

Like other members of this family, the cell surface localization allows for a better analysis of its biophysical properties. ClC-4 yields a strongly outwardly rectifying current that is inhibited by low extracellular pH; to date, the physiological relevance of pH regulation remains unclear.

In ClC-5, extracellular SCN - uncouples transport but does not affect proton transport Grieschat and Alekov, , an apparent isoform-specific effect. Thus, ClC-4 is suggested to function as a channel or exchanger depending on the extracellular anion Alekov and Fahlke, Currently, there is little scientific consensus regarding the sub-cellular localization of ClC-4 Figure 5.

On those studies, ClC-4 was found in sub-apical vesicles of proximal tubule epithelium Mohammad-Panah et al. However, none of the immunohistochemistry studies performed thus far have used cells from ClC-4 KO mice as a negative control to confirm their data.

ClC-4 was suggested to facilitate endosomal acidification by working as the electrical shunt for proton accumulation mediated by the proton pump. Although ClC-4 trafficking is similar to ClC-5, they do not appear to perform similar physiological functions Mohammad-Panah et al. One naturally occurring mutation GR , found in a patient with severe epilepsy and delayed development, nearly abolished ClC-4 currents when expressed heterologously Veeramah et al. Hu et al.

Currents of ClC-4 proteins carrying each of these mutations were much smaller or even absent compared to wild-type ClC Additional studies using specific antibodies and appropriate KO controls are necessary to further understand ClC-4 physiological function in specific cell compartments, determine precise sub-cellular localization, and investigate possible roles in human diseases.

First attempts to record ClC-6 currents by heterologous expression were frustrated by its late endosomal localization Brandt and Jentsch, ; Buyse et al.

ClC-6 mediates outwardly rectifying currents that are reduced by extracellular acidification, as in other ClC-exchangers.

ClC-6 KO mice present no apparent abnormal phenotypes, with normal life span and weight. Deposits found in ClC-6 KO mice tested positive for markers typically found in neuronal ceroid lipofuscinosis NCL , a lysosomal storage disease.

Cl - ion transport has risen from obscurity to become a vibrant and exciting field in ion transport research.

Within this field, ClC proteins are a particularly intriguing family of anion channels and transporters involved in several important physiological functions. Twenty-five years after the discovery of its first member ClC-0 , and following enormous efforts to study their biological aspects, many questions about the structure, function, and pathophysiological roles of ClCs have been answered, but an equally high number of new and, so far, unsolved questions have emerged.

For instance, the precise localization of ClC-K channels in the thin limb of the loop of Henle in the kidney and its function in intercalated cells are still unknown. Phenotypes of mouse models have linked ClC protein function and dysfunction with inherited human genetic diseases.

Useful tools to increase our knowledge about the molecular basis of ClC-related diseases would include the development of small molecules able to specifically block or activate ClC proteins. Unfortunately, currently available compounds targeting ClC proteins are few and far between, and they lack specificity. Acidification and Cl - accumulation seem not to be the only functions of ClC exchangers in these compartments. However, this may be only a matter of time; recently, leukodystrophy and azoospermia—typically phenotypes of ClC-2 KO mice—were described in patients with ClC-2 mutations.

Crystal structures of prokaryote and eukaryote ClC proteins have provided important insights about molecular structure and ion conductance mechanisms.

ClC proteins are unique in their double-barreled structure, providing a new model of ion transport in which the same basic architecture supports bona fide channel conductance and ion co-transport. These two types of ion translocation were believed to occur by entirely distinct mechanisms.

However, the available crystal structures were not sufficient to uncover the molecular mechanism governing the common gating mechanism and the precise proton transport pathway. Use of new approaches or the development of novel techniques may be necessary to uncover the molecular mechanisms underlying ClC ion transport.

Generation of crystal structures of mammalian ClC channels and exchangers will ultimately permit a more accurate investigation into the differences between these two structures, and also the identification of regions involved in interaction and modulation by other cellular components.

Moreover, those structures will greatly assist in the development of new compounds able to modify specific types of ClC proteins, thus opening the field for pharmacological approaches aiming at generating therapeutic drugs. Such drugs would have the potential to reduce or even eliminate the undesired symptoms caused by ClC proteins loss-of-function, improving quality of life for many patients. DP analyzed the literature, wrote the paper, and prepared the figures; RP analyzed the literature and reviewed the paper; VC analyzed the literature, reviewed the paper and supervised the work.

VC is a Cystic Fibrosis Canada researcher. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We thank Dr. Younes Anini, Dr. Xianping Dong, Dr. Robert Rose for insightful and critical feedback.

Accardi, A. Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels. Nature , — Adachi, S. PubMed Abstract Google Scholar. Adrian, R. On the repetitive discharge in myotonic muscle fibres. Al-Awqati, Q. Chloride channels of intracellular organelles. Cell Biol. Alekov, A. Andrini, O. ClC-K chloride channels: emerging pathophysiology of bartter syndrome type 3.

Renal Physiol. Arreola, J. Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl- channel gene. Bae, H. Protein kinase A regulates chloride conductance in endocytic vesicles from proximal tubule. Beck, C. Molecular basis for decreased muscle chloride conductance in the myotonic goat. Bennetts, B. Molecular determinants of common gating of a ClC chloride channel. Bergsdorf, E. Bezanilla, F. How membrane proteins sense voltage.

Bi, M. Chloride channelopathies of ClC Blanz, J. Leukoencephalopathy upon disruption of the chloride channel ClC Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl- channel disruption. EMBO J. Brandt, S. FEBS Lett. Bretag, A. Muscle chloride channels. Google Scholar. Brinkmeier, H. Activators of protein kinase C induce myotonia by lowering chloride conductance in muscle.

Bryant, S. Desmedt Basel: Karger Publishers , — Buyse, G. Bykova, E. Large movement in the C-terminus of CLC-0 chloride channel during slow gating. Camerino, G. Cappola, T. Basolateral ClC-2 chloride channels in surface colon epithelium: regulation by a direct effect of intracellular chloride. Gastroenterology , — Cederholm, J.

Inter-subunit communication and fast gate integrity are important for common gating in hClC Chalhoub, N. Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and human. Chen, T. Coupling gating with ion permeation in ClC channels. STKE e Chen, Y. Christensen, E. Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. Clague, M. Vacuolar ATPase activity is required for endosomal carrier vesicle formation.

Cleiren, E. Albers-schonberg disease autosomal dominant osteopetrosis, type II results from mutations in the ClCN7 chloride channel gene. De Angeli, A. De Luca, A. Opposite effects of enantiomers of clofibric acid derivative on rat skeletal muscle chloride conductance: antagonism studies and theoretical modeling of two different receptor site interactions.

Depienne, C. Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study. Lancet Neurol. Desaphy, J. Functional characterization of ClC-1 mutations from patients affected by recessive myotonia congenita presenting with different clinical phenotypes. Di Bella, D. Subclinical leukodystrophy and infertility in a man with a novel homozygous CLCN2 mutation.

Neurology 83, — Dickerson, L. Altered GABAergic function accompanies hippocampal degeneration in mice lacking ClC-3 voltage-gated chloride channels. Brain Res. Duan, D. Molecular identification of a volume-regulated chloride channel. Duffield, M. Involvement of helices at the dimer interface in ClC-1 common gating. Zinc inhibits human ClC-1 muscle chloride channel by interacting with its common gating mechanism.

Dutzler, R. X-ray structure of a CLC chloride channel at 3. Gating the selectivity filter in ClC chloride channels. Science , — Eguchi, H. Acetazolamide acts directly on the human skeletal muscle chloride channel.