Types Of Nonselective Cation Channels Research Articles

Role of TRP Channels in Metabolism-Related Diseases.

Metabolic syndrome (MetS), with its high prevalence and significant impact on cardiovascular disease, poses a substantial threat to human health. The early identification of pathological abnormalities related to MetS and prevention of the risk of associated diseases is of paramount importance. Transient Receptor Potential (TRP) channels, a type of nonselective cation channel, are expressed in a variety of tissues and have been implicated in the onset and progression of numerous metabolism-related diseases. This study aims to review and discuss the expression and function of TRP channels in metabolism-related tissues and blood vessels, and to elucidate the interactions and mechanisms between TRP channels and metabolism-related diseases. A comprehensive literature search was conducted using keywords such as TRP channels, metabolic syndrome, pancreas, liver, oxidative stress, diabetes, hypertension, and atherosclerosis across various academic databases including PubMed, Google Scholar, Elsevier, Web of Science, and CNKI. Our review of the current research suggests that TRP channels may be involved in the development of metabolism-related diseases by regulating insulin secretion and release, lipid metabolism, vascular functional activity, oxidative stress, and inflammatory response. TRP channels, as nonselective cation channels, play pivotal roles in sensing various intra- and extracellular stimuli and regulating ion homeostasis by osmosis. They present potential new targets for the diagnosis or treatment of metabolism-related diseases.

The effect of transient receptor potential vanilloid 4 on the intestinal epithelial barrier and human colonic cells was affected by tyrosine-phosphorylated claudin-7

TRPV4 is a type of nonselective cation channel, and activation of TRPV4 in the gastrointestinal tract causes experimental colitis in mice. A previous study found that tyrosine-phosphorylated claudin-7 is increased in experimental colitis. The relationship between tyrosine-phosphorylated claudin-7 and TRPV4 remains undefined. In the present study, we developed a claudin-7 mutant by replacing tyrosine with glutamic acid at position 210, named cld7-Y210E colonic cells. We found that activation of TRPV4 by GSK1016790A increased the permeability of control colonic cell monolayers, which was decreased by the TRPV4 antagonist HC067047. In monolayers of cld7-Y210E colonic cells, no differences in permeability were found between GSK1016790A and HC067047 treatments. GSK1016790A increased the aggregation of claudin-7 at the cell membrane in control colonic cells, and the effect was diminished by HC067047. In cld7-Y210E colonic cells, neither GSK1016790A nor HC067047 apparently changed the aggregation of claudin-7. Neither GSK1016790A nor HC067047 altered the TRPV4 protein level in vector colonic cells. In cld7-wild colonic cells, GSK1016790A did not alter the TRPV4 protein level, while HC067047 increased the TRPV4 protein level. The TRPV4 protein level was increased in cld7-Y210E colonic cells, decreased by GSK1016790A and further decreased by HC067047. Calcium influx was not significantly changed in the control colonic cells treated with GSK1016790A. However, GSK1016790A significantly increased calcium influx in cld7-Y210E colonic cells. We concluded that tyrosine-phosphorylated claudin-7 affects the TRPV4-modulated intestinal epithelial barrier, TRPV4-mediated calcium influx, and the protein expression of TRPV4 in human colonic cells. We suggest that tyrosine-phosphorylated claudin-7 affects the TRPV4-modulated intestinal epithelial barrier, which might be related to TRPV4 expression and TRPV4-mediated calcium influx.

Editorial: Ion Channels of Mature Human Erythrocytes

Editorial: Ion Channels of Mature Human Erythrocytes

Na+- K+ transport in roots under salt stress

Salinity causes billion dollar losses in annual crop production. So far, the main avenue in breeding crops for salt tolerance has been to reduce Na+ uptake and transport from roots to shoots. Recently we have demonstrated that retention of cytosolic K+ could be considered as another key factor in conferring salt tolerance in plants. A subsequent study has shown that Na+-induced K+ efflux in barley root epidermis occurs primarily via outward rectifying K+ channels (KORC). Surprisingly, expression of KORC was similar in salt- tolerant and sensitive genotypes. However, the former were able to better oppose Na+-induced depolarization via enhanced activity of plasma membrane H+-ATPase (thus minimizing K+ leak from the cytosol). In addition to highly K+-selective KORC channels, activities of several types of non-selective cation channels were detected at depolarizing potentials. Here we show that the expression of one of them, NORC, was significantly lower in salt-tolerant genotypes. As NORC is capable of mediating K+ efflux coupled to Na+ influx, we suggest that the restriction of its activity could be beneficial for plants under salt stress.

Characteristics of Biphasic Slow Depolarizing and Slow Hyperpolarizing Potential in Frog Taste Cell Induced by Parasympathetic Efferent Stimulation

When the velocity of capillary blood flow in the frog tongue declined to an intermediate range of 0.2-0.7 mm/s, the glossopharyngeal nerve stimulation induced a biphasic slow depolarizing and slow hyperpolarizing potential (HP) in taste cells. The objective of this work was to examine the generative mechanisms of the biphasic slow potentials. The biphasic slow response was always preceded by a slow depolarizing potential (DP) component and followed by a slow HP component. Intravenous injection of tubocurarine completely blocked the biphasic slow responses, suggesting that both components of the biphasic slow potentials are evoked by the parasympathetic nerve (PSN) fibers. Membrane conductance of taste cells increased during slow DPs and decreased during slow HPs. The reversal potential of either component of a biphasic slow response was the almost same value of -12 mV. An antagonist, L-703,606, for neurotransmitter substance P neurokinin(1) receptor completely blocked both components of the biphasic slow responses. An antagonist, flufenamic acid, for nonselective cation channels on the taste cell membrane completely blocked the biphasic slow responses. These results suggest that PSN-induced biphasic slow responses are postsynaptically elicited in taste cells by releasing substance P at the PSN axon terminals. It is concluded that the slow DP component may be generated by opening one type of nonselective cation channel on taste cells and that the slow HP component may be generated by closing the other type of nonselective cation channel. We discussed that a second messenger inositol 1,4,5-trisphosphate might be related to a slow DP component and another second messenger diacylglycerol might be related to a slow HP component.

Agonist and antagonist sensitivity of non‐selective cation channel currents evoked by muscarinic receptor stimulation in bovine ciliary muscle cells

1 In the bovine ciliary muscle, stimulation of muscarinic receptors with carbachol (CCh) opens two types of non-selective cation channels (NSCCS and NSCCL) with widely different unitary conductances (100 fS and 35 pS). Here we examined the dependence of the activity of NSCCS on the agonist (CCh) concentration by whole-cell voltage clamp in freshly isolated bovine ciliary muscle cells. We also examined the sensitivity of CCh-evoked NSCCS currents to several muscarinic receptor antagonists. 2 The voltage clamp experiments were carried out using Ba2+ as the charge carrier, as this divalent cation is the most permeant for NSCCS of the alkali and alkaline earth metal ions hitherto examined, whereas it is relatively impermeant to NSCCL. For the dose-activation relationship obtained, the apparent dissociation constant K was estimated to be 0.5 +/- 0.2 microm (n = 31), a value of an order of magnitude smaller than the one reported for CCh-evoked NSCCL currents in our previous experiments. 3 In the dose-inhibition experiments we observed that the CCh-evoked NSCCS currents were inhibited by the muscarinic antagonists with the following potency sequence: atropine approximately 4-DAMP >> pirenzepine > AF-DX116, indicating that the activation of NSCCS by CCh is mediated by an M3 muscarinic receptor. 4 We have previously shown by reverse transcriptase-polymerase chain reaction that the bovine ciliary muscle contains mRNAs for several transient receptor potential channel homologues (TRPC1, TRPC3, TRPC4 and TRPC6) which are attracting attention as molecular candidates for receptor-operated NSCCs. In the present experiments, we succeeded in visually identifying these TRPCs in the plasma membrane of cultured bovine ciliary muscle cells by immunofluorescence microscopy.

Sodium influx and accumulation in Arabidopsis.

Arabidopsis is frequently used as a genetic model in plant salt tolerance studies, however, its physiological responses to salinity remain poorly characterized. This study presents a characterization of initial Na+ entry and the effects of Ca2+ on plant growth and net Na+ accumulation in saline conditions. Unidirectional Na+ influx was measured carefully using very short influx times in roots of 12-d-old seedlings. Influx showed three components with distinct sensitivities to Ca2+, diethylpyrocarbonate, and osmotic pretreatment. Pharmacological agents and known mutants were used to test the contribution of different transport pathways to Na+ uptake. Influx was stimulated by 4-aminobutyric acid and glutamic acid; was inhibited by flufenamate, quinine, and cGMP; and was insensitive to modulators of K+ and Ca2+ channels. Influx did not differ from wild type in akt1 and hkt1 insertional mutants. These data suggested that influx was mediated by several different types of nonselective cation channels. Na+ accumulation in plants grown in 50 mM NaCl was strongly reduced by increasing Ca2+ activity (from 0.05-3.0 mM), and plant survival was improved. However, plant biomass was not affected by shoot Na+ concentration, suggesting that in Arabidopsis Na+ toxicity is not dependent on shoot Na+ accumulation. These data suggest that Arabidopsis is a good model for investigation of Na+ transport, but may be of limited utility as a model for the study of Na+ toxicity.

Nonselective Cation Channels of the Plasma Membrane.

Nonselective cation channels (NSCCs) are defined as the channel exhibiting better selectivity for cations over anions. This nomenclature is however confusing, because the channels which fall into this category show a high degree of heterogeneity in their biophysics, physiology and pharmacology. Since little molecular information is yet available for most types of NSCC (except for the fast extracellular ligand-gated NSCC), one useful criterion to sub-classify them is the mode of activation. Based on this, more than 10 subclasses of NSCC, including the G-protein-coupled NSCC as a newly emerging member, can be distinguished (Table 1). Furthermore, the biophysical and pharmacological profile of these subclasses of NSCC suggest that varying extents of structural similarities may exist. Such a duality, i.e. heterogeneity and similarity of NSCC is on one hand, the obstacle to exploiting selective drugs for NSCCs, but on the other hand, may account for a broad repertoire of functions that NSCCs subserve under various patho-physiological conditions. This short paper briefly overviews, from such an aspect, the physiology and pharmacology of NSCCs of the plasma membrane, which have rather poorly been elucidated so far.

A novel large conductance, nonselective cation channel in pheochromocytoma (PC12) cells.

A new type of nonselective cation channel was identified and characterized in pheochromocytoma (PC12) cells using inside-out and cell-attached patch-clamp recordings. The channel shows a large unitary conductance (274 pS in symmetric 145 mm K+) and selectivity for Na+ approximately K+ > Li+, and is practically impermeable to Cl-. The channel activity-voltage relationship is bell-shaped, showing maximal activation at approximately -10 mV. The overall activity of this channel is unmodified by [Na+]ic, or [Ca++]ic. However, increases in [Ca++]ic lead to a decrease in the unitary current amplitude. In addition, overall activity is mildly increased when suction is applied to the back of the patch pipette. Together, these characteristics distinguish the present channel from all other large conductance nonselective cation channels reported so far in a variety of preparations. The frequency of appearance of this channel type is similar in undifferentiated and NGF-treated PC12 cells ( approximately 8-27% of patches). The combination of large conductance, permeability to Na+, and existence of conducting states at negative potentials, may provide a significant pathway for inward current and depolarization in PC12 cells.

Classification of ion channels in the luminal and abluminal membranes of guinea‐pig endocardial endothelial cells.

1. The ion channels on both the luminal and abluminal membranes of endocardial endothelial (EE) cells were separately recorded using the patch clamp technique in the guinea-pig heart. 2. The major population consisted of two types of non-selective cation channels, which showed open probabilities of 0.21 and 0.33 at the resting potential, and conductances of 36 and 11 pS, respectively. 3. The next major class was Cl- channels with an ohmic conductance of 409 pS. The channel was quiescent in the cell-attached mode but was activated by strong depolarization after excising the patch membrane. 4. The channels activated by intracellular Ca2+ were mainly K+ channels showing a 34 pS slope conductance and, less frequently, Ca(2+)-dependent K+ channels having a large conductance (210 pS). The inward rectifier K+ channel (32 pS) was also observed. 5. The non-selective cation channels were recorded on the luminal membrane, but scarcely on the abluminal membrane, suggesting an active transport of K+ and Na+ across the endocardium. 6. The resting membrane conductance of the EE cells may be provided mostly by non-selective cation channels and 34 pS Ca(2+)-dependent K+ channels.

Mesangial cell ion transport and tubuloglomerular feedback.

Mesangial cells possess Ca(2+)-activated Cl- channels, Ca(2+)-activated K+ channels, voltage-gated Ca2+ channels, ATP-sensitive K+ channels, and two types of nonselective cation channels. Angiotensin II and arginine vasopressin depolarize the membrane. This membrane depolarization is caused by the activation of Ca(2+)-activated Cl- and Ca(2+)-activated nonselective cation channels through an elevation of intracellular Ca2+ concentration. The Ca(2+)-independent nonselective cation channel is activated by platelet-derived growth factor and is a candidate for the receptor-activated Ca2+ influx system. It has been suggested that macula densa Cl- reabsorption determines the Cl- concentration of juxtaglomerular apparatus interstitial fluid and thereby affects the resistance of afferent arterioles. In addition, angiotensin II-mediated and arginine vasopressin-mediated mesangial cell Ca2+ signals and contraction are attenuated via prostaglandin production by the mesangial cells themselves when the ambient Cl- concentration is reduced. Thus, Cl- plays an essential role in the tubuloglomerular feedback mechanism. The intracellular Ca2+ concentration appears to be important for the signal transduction mechanism of tubuloglomerular feedback. The ionic channels on the mesangial cell membrane may participate in controlling the intracellular Ca2+ concentration. The association of disturbed tubuloglomerular feedback and the development of hypertension has recently been reported.

Voltage-dependent L-type Ca channels and a novel type of non-selective cation channel activated by cAMP-dependent phosphorylation in mesoderm-like (MES-1) cells

Undifferentiated P19 embryonal carcinoma cells (ECC P19), the P19-derived clonal cell lines END-2 (visceral endoderm-like), EPI-7 (epithelioid ectoderm-like), MES-1 (mesoderm-like) and a parietal yolk sac cell line (PYS-2) were used as cellular models to examine the functional expression of voltage-dependent Ca channels and other Ca-permeable cation channels at various stages of early embryonic development. Whole-cell currents were recorded by means of the patch clamp technique. Whereas more than 75% of MES-1 cells possessed Ca channel currents, neither P19, END-2, EPI-7 nor PYS-2 cells had detectable voltage-dependent inward currents. Ca channel currents of MES-1 cells were highly sensitive towards 1,4-dihydropyridines and blocked by cadmium. Adrenaline (10 μM) caused Ca channel stimulation in only 14% of MES-1 cells examined. However, in 62% of the cells adrenaline activated a linear current component which under physiological conditions reversed close to 0 mV. Removal of extracellular Na + suppressed the adrenaline-induced inward current, while reducing extracellular Cl − had no significant effect. These findings suggest that the adrenaline-induced current is carried through non-selective cation channels which were found to be permeable for Na +, K +, Cs + å Ca 2+. Remarkably, the intracellular signalling pathway for activation of the non-selective cation current involved the cascade of reactions leading to cAMP-dependent phosphorylation, a regulatory pathway well known for cardiac Ca channels. A possible functional role of adrenaline-induced non-selective cation currents and Ca channels in embryonal development is discussed.

Physiology of muscarinic receptor-operated nonselective cation channels in guinea-pig ileal smooth muscle.

Stimulations of autonomic nerves in smooth muscle often evoke both fast and slow excitatory junction potentials (EJPs), which are thought to involve activations of several distinct types of nonselective cation channels (NSC channels). The ACh-activated NSC channel in guinea-pig ileum (I(ns), ACh) is one probably responsible for the slow EJP and seems to undergo various regulations. This short paper will review the physiology of I(ns),ACh, with particular emphasis on its dynamic interactions with other physiologically important factors such as the membrane potential, [Ca2+]i and pH.

Cation channels in oocytes and early states of development: a novel type of nonselective cation channel activated by adrenaline in a clonal mesoderm-like cell line (MES-1).

The expression of receptors and ion channels alters during growth, maturation, and after fertilization of oocytes reflecting functional changes. Besides voltage-dependent ion channels, oocyte membranes possess an IP3-activated cation channel mediating a prolonged Ca2+ influx. The Ca2+ is thought to be involved in maturation and fertilization. Alternatively, mono- and divalent cations can enter oocytes via stretch-activated channels. The oocyte channel population is further modified during subsequent embryogenesis, suggesting that ionic channels obviously become expressed at specific states of embryological differentiation and in tissue-specific manner. The resulting differences in functional ion channel populations of adult cells underlie the large diversity of cells and their function. Conversely, differentiation and cell proliferation themselves depend on ion transport. Ca2+ ions have been shown to play a pivotal role in these processes. Nonselective cation channels represent one possible pathway for Ca2+ entry into the cell and, therefore, might be involved in the regulation of embryological development. Undifferentiated embryonal carcinoma cells (P19), visceral endoderm-like cells (END-2), epithelioid ectoderm-like cells (EPI-7), mesoderm-like cells (MES-1), and parietal yolk sac cells (PYS-2) have been used as a model to study the expression of ionic channels during early development. In MES-1 cells a nonselective cation current was activated by adrenaline. Interestingly, the intracellular pathway for activation of these channels involved the cascade of activation of the cAMP-dependent protein kinase (PKA) resulting in protein phosphorylation. This mechanism is well known for Ca2+ channel stimulation in cardiac and skeletal muscle both originating from the mesoderm.

Non-selective cationic channel in primary cultured cells of brown adipose tissue

Single channel current events were recorded from membranes of cultured brown adipose tissue cells with the patch-clamp technique. In excised inside-out patches the predominant type of events showed a slope conductance of about 30 pS (25 degrees C). The current was carried by both, Na+ ions and K+ ions. Discrimination between them was poor. The frequency of events increased with increasing temperature. Their amplitude was temperature dependent as well (Q10 approximately equal to 1.4). A single exponential was not sufficient for fitting the histograms of "on-time" or "off-time". We conclude that these events belong to a type of non-selective cation channel described previously for other tissues.

Antibody activates cationic channels via second messenger Ca 2+

Patch-clamp recordings were used to study single channels permeable to multiple cations in a macrophage cell line. At least three conductance levels were found, consistent with the existence of several types of nonselective cation channels or a single channel with multiple open states. The activity of the channels depended very little on voltage but was affected by internal Ca 2+ concentration. Specific subclasses of immunoglobulins (IgG1 and IgG2b) bound to an Fc receptor on the surface of these macrophages. When an IgG2b was applied to the cell exterior after a patch pipette had been sealed in the cell-attached mode, the nonselective cation channels within the patch were activated. Thus, these channels must be modulated by a second messenger. Since antibodies binding to the Fc receptor have been shown to produce a rise in intracellular Ca 2+, this cation must be considered a candidate as a second messenger that amplifies the effect of antibody in gating these channels.