A Comparison of the Effect of Lead (Pb) on the Slow Vacuolar (SV) and Fast Vacuolar (FV) Channels in Red Beet (Beta vulgaris L.) Taproot Vacuoles

Little is known about the effect of lead on the activity of the vacuolar K⁺ channels. Here, the patch-clamp technique was used to compare the impact of lead (PbCl₂) on the slow-activating (SV) and fast-activating (FV) vacuolar channels. It was revealed that, under symmetrical 100-mM K⁺, the macroscopic currents of the SV channels exhibited a typical slow activation and a strong outward rectification of the steady-state currents, while the macroscopic currents of the FV channels displayed instantaneous currents, which, at the positive potentials, were about three-fold greater compared to the one at the negative potentials. When PbCl₂ was added to the bath solution at a final concentration of 100 µM, it decreased the macroscopic outward currents of both channels but did not change the inward currents. The single-channel recordings demonstrated that cytosolic lead causes this macroscopic effect by a decrease of the single-channel conductance and decreases the channel open probability. We propose that cytosolic lead reduces the current flowing through the SV and FV channels, which causes a decrease of the K⁺ fluxes from the cytosol to the vacuole. This finding may, at least in part, explain the mechanism by which cytosolic Pb²⁺ reduces the growth of plant cells.     

The Apoptotic Volume Decrease Is an Upstream Event of MAP Kinase Activation during Staurosporine-Induced Apoptosis in HeLa Cells

Persistent cell shrinkage, called apoptotic volume decrease (AVD), is a pivotal event of apoptosis. Activation of the volume-sensitive outwardly rectifying Cl(-) channel (VSOR) is involved in the AVD induction. On the other hand, activation of the MAP kinase (MAPK) cascade is also known to play a critical role in apoptosis. In the present study, we investigated the relationship between the AVD induction and the stress-responsive MAPK cascade activation during the apoptosis process induced by staurosporine (STS) in HeLa cells. STS was found to induce AVD within 2-5 min and phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK after over 20-30 min. VSOR blockers suppressed not only STS-induced AVD but also phosphorylation of JNK and p38 as well as activation of caspase-3/7. Moreover, a p38 inhibitor, SB203580, and a JNK inhibitor, SP600125, failed to affect STS-induced AVD, whereas these compounds reduced STS-induced activation of caspase-3/7. Also, treatment with ASK1-specific siRNA suppressed STS-induced caspase-3/7 activation without affecting the AVD induction. Furthermore, sustained osmotic cell shrinkage per se was found to trigger phosphorylation of JNK and p38, caspase activation, and cell death. Thus, it is suggested that activation of p38 and JNK is a downstream event of AVD for the STS-induced apoptosis of HeLa cells.     

Functional studies of synthetic gramicidin hybrid ion channels in CHO cells

The function of a gramicidin hybrid ion channel in living Chinese hamster ovary (CHO) cells was investigated by the patch clamp method. The synthetic ion channel 1 consists of two cyclohexyl ether amino acids that link two mini-gramicidin strands. With 1 at a concentration of 1.0 microM, an increase in the whole-cell membrane conductance was observed after 1.37 min. The conductance showed larger currents when Cs(+) was used as charge carrier than when Na(+) and K(+) were used. In single-channel recordings with Cs(+) as charge carrier, the substance showed comparable single-channel amplitudes in the membrane of living cells and artificial black lipid bilayers. In addition to functioning as a cation channel, compound 1 appeared to be a water channel. Exposure of the CHO cells to an extracellular hypoosmotic solution did not substantially change the cell volume. Extracellular hypoosmotic conditions in the presence of 1 increased the cell size to 146.5 % that of the control. Thus, the synthetic hybrid channel 1 can function as a cation channel with some Cs(+) specificity, and as a water channel in CHO cells.     

Electrophysiological Properties of Endogenous Single Ca2+ Activated Cl− Channels Induced by Local Ca2+ Entry in HEK293

Microdomains formed by proteins of endoplasmic reticulum and plasma membrane play a key role in store-operated Ca²⁺ entry (SOCE). Ca²⁺ release through inositol 1,4,5-trisphosphate receptor (IP₃R) and subsequent Ca²⁺ store depletion activate STIM (stromal interaction molecules) proteins, sensors of intraluminal Ca²⁺, which, in turn, open the Orai channels in plasma membrane. Downstream to this process could be activated TRPC (transient receptor potential-canonical) calcium permeable channels. Using single channel patch-clamp technique we found that a local Ca²⁺ entry through TRPC1 channels activated endogenous Ca²⁺-activated chloride channels (CaCCs) with properties similar to Anoctamin6 (TMEM16F). Our data suggest that their outward rectification is based on the dependence from membrane potential of both the channel conductance and the channel activity: (1) The conductance of active CaCCs highly depends on the transmembrane potential (from 3 pS at negative potentials till 60 pS at positive potentials); (2) their activity (NPo) is enhanced with increasing Ca²⁺ concentration and/or transmembrane potential, conversely lowering of intracellular Ca²⁺ concentration reduced the open state dwell time; (3) CaCC amplitude is only slightly increased by intracellular Ca²⁺ concentration. Experiments with Ca²⁺ buffering by EGTA or BAPTA suggest close local arrangement of functional CaCCs and TRPC1 channels. It is supposed that Ca²⁺-activated chloride channels are involved in Ca²⁺ entry microdomains.     

2,4,6,4＇-四羟基脱氧安息香的合成及其抑制酪氨酸酶活性的研究

合成2,4,6,4'-四羟基脱氧安息香(THDB),对其抑制酪氨酸酶活性进行评价。在无水氯化锌和氯化氢存在下,以间苯三酚和对羟基苯乙腈为原料,进行THDB的合成,并对所得化合物在0.05%、0.10%、0.20%、0.25%、0.30%、0.35%、0.40%七个浓度下与根皮素、熊果苷和曲酸进行抑制酪氨酸酶对比实验。收率由原来报导的46.5%提高到60.0%,在0.4%浓度时THDB对酪氨酸酶的抑制率达98.2%。本工艺是合成THDB的较佳工艺,THDB对酪氨酸酶的抑制作用比熊果苷和曲酸好,与根皮素相当。     

An Electrophysiological Comparison of Voltage-Gated Proton Channels,Other Ion Channels,and Other Proton Channels

Voltage-gated proton selective channels occupy an ill-defined region between “normal” ion channels and a variety of proton-conducting pathways inside proteins, including, but not limited to, membrane-bound proteins. Voltage-gated H⁺ channels closely resemble other voltage-gated ion channels in their voltage- and time-dependent gating, but differ in their extreme selectivity, their miniscule single-channel conductance, and the high activation enthalpy for conduction. Furthermore, in contrast with the “multiple occupancy” hypothesized to account for aspects of permeation through other ion channels, it seems unlikely that H⁺ channels can be occupied by more than one proton at a time. Voltage-gated H⁺ channels functionally resemble other proton-conducting pathways in proteins, but until their structure has been determined, this similarity will remain speculative. The present restriction to functional measurements is less of a handicap than might be expected—the history of ion channel research shows that deductions based on electrophysiological measurements often closely predict the eventually determined structure. Existing evidence supports the idea that protons permeate the membrane through voltage-gated H⁺ channels by hopping across a hydrogen-bonded chain that consists of at least some amino acid side groups in addition to water molecules.     

Exploring the pharmacology and action spectra of photochromic open-channel blockers

Light control of voltage-gated ion channels: We have developed red-shifted derivatives of QAQ, a powerful doubly charged photochromic blocker. These derivatives allow for remote control of K(v) and Na(v) channel conductance with light and offer the opportunity to silence neuronal activity reversibly.     

Optimization of methane reforming in a microreactor—effects of catalyst loading and geometry

In this paper, the effect of the catalyst surface site density (catalyst amount) and reactor geometry on the reforming process of methane in a wall-coated, single-channel microreactor is investigated numerically. Such a reactor, consisting of a tubular flow channel and a thermal conductive channel wall, is a good representation of microfabricated channels and monoliths. It is found that the hydrogen selectivity changes significantly with varying catalyst loading, which is a noteworthy result. Thus, the reaction path leading to higher hydrogen production becomes more important by increasing the catalyst surface site density on the active surface. This is due to the splitting rate of methane and water, which is a function of catalyst density. Furthermore, this study shows the significance of scaling the inlet volume flow not only with the reactor volume (gas space velocity) but also with the catalyst amount (catalyst space velocity). Another unexpected result is the presence of an optimum channel geometry and an optimum catalyst amount if the gas space velocity and the catalyst space velocity are constant. This underlines the necessity of coordinating the channel diameter, the inlet volume flow rate, and the catalyst amount in order to obtain a maximum reformer performance. Furthermore, it is necessary to specify the catalyst amount, the inlet conditions and the geometry in order to characterize sufficiently a catalytic reactor.     

Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice

Dry eye disease is one of the most common diseases, with increasing prevalence in many countries, but treatment options are limited. Cystic fibrosis transmembrane conductance regulator (CFTR) is a major ion channel that facilitates fluid secretion in ocular surface epithelium and is a potential target of therapeutic agent for the treatment of dry eye disease. In this study, we performed a cell-based, high-throughput screening for the identification of novel natural products that activate CFTR and restore the aqueous deficiency in dry eye. Screening of 1000 natural products revealed isorhamnetin, a flavonol aglycone, as a novel CFTR activator. Electrophysiological studies showed that isorhamnetin significantly increased CFTR chloride current, both wild type and ∆F508-CFTR. Isorhamnetin did not alter intracellular cAMP levels and the activity of other ion channels, including ANO1, ENaC, and hERG. Notably, application of isorhamnetin on mouse ocular surface induced CFTR activation and increased tear volume. In addition, isorhamnetin significantly reduced ocular surface damage and expression of interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α in an experimental mouse model of dry eye. These data suggest that isorhamnetin may be used to treat dry eye disease.     

Evidence for P-Glycoprotein Involvement in Cell Volume Regulation Using Coulter Sizing in Flow Cytometry

The regulation of cell volume is an essential function that is coupled to a variety of physiological processes such as receptor recycling, excitability and contraction, cell proliferation, migration, and programmed cell death. Under stress, cells undergo emergency swelling and respond to such a phenomenon with a regulatory volume decrease (RVD) where they release cellular ions, and other osmolytes as well as a concomitant loss of water. The link between P-glycoprotein, a transmembrane transporter, and cell volume regulation is controversial, and changes in cells volume are measured using microscopy or electrophysiology. For instance, by using the patch-clamp method, our team demonstrated that chloride currents activated in the RVD were more intense and rapid in a breast cancer cell line overexpressing the P-glycoprotein (P-gp). The Cell Lab Quanta SC is a flow cytometry system that simultaneously measures electronic volume, side scatter and three fluorescent colors; altogether this provides unsurpassed population resolution and accurate cell counting. Therefore, here we propose a novel method to follow cellular volume. By using the Coulter-type channel of the cytometer Cell Lab Quanta SC MPL (multi-platform loading), we demonstrated a role for the P-gp during different osmotic treatments, but also a differential activity of the P-gp through the cell cycle. Altogether, our data strongly suggests a role of P-gp in cell volume regulation.     

Evidence for Dual Activation of IK(M) and IK(Ca) Caused by QO-58 (5-(2,6-Dichloro-5-fluoropyridin-3-yl)-3-phenyl-2-(trifluoromethyl)-1H-pyrazolol[1,5-a]pyrimidin-7-one)

QO-58 (5-(2,6-dichloro-5-fluoropyridin-3-yl)-3-phenyl-2-(trifluoromethyl)-1H-pyrazolol[1,5-a]pyrimidin-7-one) has been regarded to be an activator of K_V7 channels with analgesic properties. However, whether and how the presence of this compound can result in any modifications of other types of membrane ion channels in native cells are not thoroughly investigated. In this study, we investigated its perturbations on M-type K⁺ current (I_K(M)), Ca²⁺-activated K⁺ current (I_K(Ca)), large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels, and erg-mediated K⁺ current (I_K(erg)) identified from pituitary tumor (GH₃) cells. Addition of QO-58 can increase the amplitude of I_K(M) and I_K(Ca) in a concentration-dependent fashion, with effective EC₅₀ of 3.1 and 4.2 μM, respectively. This compound could shift the activation curve of I_K(M) toward a leftward direction with being void of changes in the gating charge. The strength in voltage-dependent hysteresis (V_hys) of I_K(M) evoked by upright triangular ramp pulse (V_ramp) was enhanced by adding QO-58. The probabilities of M-type K⁺ (K_M) channels that will be open increased upon the exposure to QO-58, although no modification in single-channel conductance was seen. Furthermore, GH₃-cell exposure to QO-58 effectively increased the amplitude of I_K(Ca) as well as enhanced the activity of BK_Ca channels. Under inside-out configuration, QO-58, applied at the cytosolic leaflet of the channel, activated BK_Ca-channel activity, and its increase could be attenuated by further addition of verruculogen, but not by linopirdine (10 μM). The application of QO-58 could lead to a leftward shift in the activation curve of BK_Ca channels with neither change in the gating charge nor in single-channel conductance. Moreover, cell exposure of QO-58 (10 μM) resulted in a minor suppression of I_K(erg) amplitude in response to membrane hyperpolarization. The docking results also revealed that there are possible interactions of the QO-58 molecule with the KCNQ or K_Ca1.1 channel. Overall, dual activation of I_K(M) and I_K(Ca) caused by the presence of QO-58 eventually may have high impacts on the functional activity (e.g., anti-nociceptive effect) residing in electrically excitable cells. Care must be exercised when interpreting data generated with QO-58 as it is not entirely KCNQ/K_V7 selective.     

Size and shape controllable synthesis and luminescent properties of BaGdF5:Ce3+/Ln3+ (Ln = Sm, Dy, Eu, Tb) nano/submicrocrystals by a facile hydrothermal process

In this paper, we present a facile and environmentally-friendly hydrothermal process to synthesize BaGdF(5): 2.5 mol% Ce(3+)/2.5 mol% Ln(3+) (Ln = Sm, Dy, Eu and Tb) nano/submicroparticles. X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), as well as photoluminescence (PL) spectra are used to characterize the resulting samples. The size, shape, and composition of the products could be tuned just by varying the organic additives and the pH values of the initial reaction solutions. The morphologies for the products include nanospheres, submicrospheres, peanut-like particles, as well as the spindle-like and star-like aggregates. Moreover, the size of the samples can be tuned from 50 nm to 150 nm. Additionally, we systematically investigate the luminescence properties of different lanthanide ions in BaGdF(5) host. Under single-wavelength excitation at 260 nm, the samples doped with different lanthanide ions show intensive multicolor visible emissions depending on the doped Ln(3+) ions. The luminescence process can be attributed to the strong absorption of UV irradiation by Ce(3+) ions, followed by energy transfer to Gd(3+) ions, from which the energy is transferred to Ln(3+), resulting in the emission from the luminescent Ln(3+) centers. The Gd(3+) ions play an intermediate role in this process.     

十二烷基硫酸钠的临界胶束浓度的测定及影响分析

临界胶束浓度(CMC)是表面活性剂活性的度量。采用电导法测定表面活性剂十二烷基硫酸钠的临界胶束浓度,并探讨了温度、NaCl或乙醇等对临界胶束浓度的影响。随着温度的升高,CMC增大;NaCl的加入量增大时,CMC在较低浓度下增大,在0.2~0.8 mmol/L范围内CMC随NaCl的量增大而降低;乙醇的加入量随体积比从0%~2.5%增大时,CMC增大,并分析了SDS的CMC发生变化的原因。     

冰点下降法测定注射用胸腺肽的渗透压

目的采用冰点下降法测定注射用胸腺肽的渗透压,并观察其稳定性。方法用制备的0.9%NaCl和5%葡萄糖标准溶液对渗透压摩尔测定仪进行标定后,连续测定5次注射用胸腺肽的渗透压,计算变异系数(CV),验证该方法的精密度;取20批注射用胸腺肽,每瓶分别用500 ml和125 ml 0.9%NaCl溶液及5%葡萄糖溶液稀释,测定其渗透压;将注射用胸腺肽分别置(6±2)℃放置12个月,(25±2)℃放置6个月,分别于不同时间取样,稀释后测定渗透压,观察其长期和加速稳定性。结果 5次测得的注射用胸腺肽渗透压的变异系数为0.401%。20批注射用胸腺肽的渗透压在287～347 mOsmol/kg之间,以不同体积的0.9%NaCl和5%葡萄糖稀释样品后测得的渗透压的变异系数均较小,表明样品的渗透压批间差异较小;在稀释液量相同的条件下,5%葡萄糖试验组的渗透压显著高于0.9%NaCl组(P均<0.001)。注射用胸腺肽分别于(6±2)℃下放置12个月和(25±2)℃、相对湿度(60±10)%的条件下放置6个月,其渗透压均无显著变化。结论冰点下降法操作简便、快速,精密度高,可用于注射用胸腺肽渗透压的检测。     

Room temperature synthesis of hydrophilic Ln(3+)-doped KGdF4 (Ln = Ce, Eu, Tb, Dy) nanoparticles with controllable size: energy transfer, size-dependent and color-tunable luminescence properties

In this paper, we demonstrate a simple, template-free, reproducible and one-step synthesis of hydrophilic KGdF(4): Ln(3+) (Ln = Ce, Eu, Tb and Dy) nanoparticles (NPs) via a solution-based route at room temperature. X-Ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), photoluminescence (PL) and cathodoluminescence (CL) spectra are used to characterize the samples. The results indicate that the use of water-diethyleneglycol (DEG) solvent mixture as the reaction medium not only allows facile particle size control but also endows the as-prepared samples with good water-solubility. In particular, the mean size of NPs is monotonously reduced with the increase of DEG content, from 215 to 40 nm. The luminescence intensity and absolute quantum yields for KGdF(4): Ce(3+), Tb(3+) NPs increase remarkably with particle sizes ranging from 40 to 215 nm. Additionally, we systematically investigate the magnetic and luminescence properties of KGdF(4): Ln(3+) (Ln = Ce, Eu, Tb and Dy) NPs. They display paramagnetic and superparamagnetic properties with mass magnetic susceptibility values of 1.03 × 10(-4) emu g(-1)·Oe and 3.09 × 10(-3) emu g(-1)·Oe at 300 K and 2 K, respectively, and multicolor emissions due to the energy transfer (ET) process Ce(3+)→ Gd(3+)→ (Gd(3+))(n)→ Ln(3+), in which Gd(3+) ions play an intermediate role in this process. Representatively, it is shown that the energy transfer from Ce(3+) to Tb(3+) occurs mainly via the dipole-quadrupole interaction by comparison of the theoretical calculation and experimental results. This kind of magnetic/luminescent dual-function materials may have promising applications in multiple biolabels and MR imaging.     

GPR37 Receptors and Megalencephalic Leukoencephalopathy with Subcortical Cysts

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of vacuolating leukodystrophy (white matter disorder), which is mainly caused by defects in MLC1 or glial cell adhesion molecule (GlialCAM) proteins. In addition, autoantibodies to GlialCAM are involved in the pathology of multiple sclerosis. MLC1 and GLIALCAM genes encode for membrane proteins of unknown function, which has been linked to the regulation of different ion channels and transporters, such as the chloride channel VRAC (volume regulated anion channel), ClC-2 (chloride channel 2), and connexin 43 or the Na⁺/K⁺-ATPase pump. However, the mechanisms by which MLC proteins regulate these ion channels and transporters, as well as the exact function of MLC proteins remain obscure. It has been suggested that MLC proteins might regulate signalling pathways, but the mechanisms involved are, at present, unknown. With the aim of answering these questions, we have recently described the brain GlialCAM interactome. Within the identified proteins, we could validate the interaction with several G protein-coupled receptors (GPCRs), including the orphan GPRC5B and the proposed prosaposin receptors GPR37L1 and GPR37. In this review, we summarize new aspects of the pathophysiology of MLC disease and key aspects of the interaction between GPR37 receptors and MLC proteins.     

Structural Modelling of KCNQ1 and KCNH2 Double Mutant Proteins,Identified in Two Severe Long QT Syndrome Cases,Reveals New Insights into Cardiac Channelopathies

Congenital long QT syndrome (LQTS) is a cardiac channelopathy characterized by a prolongation of the QT interval and T-wave abnormalities, caused, in most cases, by mutations in KCNQ1, KCNH2, and SCN5A. Although the predominant pattern of LQTS inheritance is autosomal dominant, compound heterozygous mutations in genes encoding potassium channels have been reported, often with early disease onset and more severe phenotypes. Since the molecular mechanisms underlying severe phenotypes in carriers of compound heterozygous mutations are unknown, it is possible that these compound mutations lead to synergistic or additive alterations to channel structure and function. In this study, all-atom molecular dynamic simulations of KCNQ1 and hERG channels were carried out, including wild-type and channels with compound mutations found in two patients with severe LQTS phenotypes and limited family history of the disease. Because channels can likely incorporate different subunit combinations from different alleles, there are multiple possible configurations of ion channels in LQTS patients. This analysis allowed us to establish the structural impact of different configurations of mutant channels in the activated/open state. Our data suggest that channels with these mutations show moderate changes in folding energy (in most cases of stabilizing character) and changes in channel mobility and volume, differentiating them from each other and from WT. This would indicate possible alterations in K⁺ ion flow. Hetero-tetrameric mutant channels showed intermediate structural and volume alterations vis-à-vis homo-tetrameric channels. These findings support the hypothesis that hetero-tetrameric channels in patients with compound heterozygous mutations do not necessarily lead to synergistic structural alterations.     

Photo‐responsive monoolein cubic phase incorporating hydrophobically modified poly(vinyl alcohol)–coumarin conjugate

Photo‐responsive monoolein cubic phases were developed by immobilizing hydrophobically modified poly (vinyl alcohol)–epoxypropoxy coumarin conjugate (HmPVA–EPC) in the water channels of the cubic phase. On the NMR spectrum of HmPVA‐EPC, the molar ratio of PVA/decanoyl chloride (a hydrophobic anchor)/EPC was determined to be about 1:0.64:1.45. The interfacial activity of PVA–EPC conjugate was much lower than that of PVA, but the interfacial activity of HmPVA–EPC was as high as that of PVA. The critical micelle concentrations of HmPVA–EPC and PVA were about 0.005%. Under the ultraviolet (UV) irradiation (λ = 254 nm), EPC residues of HmPVA were readily dimerized and the dimerization degree in 180 min was about 33%. The irradiation of UV light had no significant effect on the release of fluorescein isothiocyanate–dextran (a fluorescence marker) from cubic phase free of polymer and cubic phase incorporating HmPVA, but it suppressed the release from cubic phase incorporating HmPVA–EPC. The photo crosslinking of HmPVA–EPC in the water channels is believed to be responsible for the suppressed release. POLYM. ENG. SCI., 54:227–233, 2014. © 2013 Society of Plastics Engineers     

Permissive Modulation of Sphingosine-1-Phosphate-Enhanced Intracellular Calcium on BKCa Channel of Chromaffin Cells

Sphingosine-1-phosphate (S1P), is a signaling sphingolipid which acts as a bioactive lipid mediator. We assessed whether S1P had multiplex effects in regulating the large-conductance Ca²⁺-activated K⁺ channel (BK_Ca) in catecholamine-secreting chromaffin cells. Using multiple patch-clamp modes, Ca²⁺ imaging, and computational modeling, we evaluated the effects of S1P on the Ca²⁺-activated K⁺ currents (I_K(Ca)) in bovine adrenal chromaffin cells and in a pheochromocytoma cell line (PC12). In outside-out patches, the open probability of BK_Ca channel was reduced with a mean-closed time increment, but without a conductance change in response to a low-concentration S1P (1 µM). The intracellular Ca²⁺ concentration (Ca_i) was elevated in response to a high-dose (10 µM) but not low-dose of S1P. The single-channel activity of BK_Ca was also enhanced by S1P (10 µM) in the cell-attached recording of chromaffin cells. In the whole-cell voltage-clamp, a low-dose S1P (1 µM) suppressed I_K(Ca), whereas a high-dose S1P (10 µM) produced a biphasic response in the amplitude of I_K(Ca), i.e., an initial decrease followed by a sustained increase. The S1P-induced I_K(Ca) enhancement was abolished by BAPTA. Current-clamp studies showed that S1P (1 µM) increased the action potential (AP) firing. Simulation data revealed that the decreased BK_Ca conductance leads to increased AP firings in a modeling chromaffin cell. Over a similar dosage range, S1P (1 µM) inhibited I_K(Ca) and the permissive role of S1P on the BK_Ca activity was also effectively observed in the PC12 cell system. The S1P-mediated I_K(Ca) stimulation may result from the elevated Ca_i, whereas the inhibition of BK_Ca activity by S1P appears to be direct. By the differentiated tailoring BK_Ca channel function, S1P can modulate stimulus-secretion coupling in chromaffin cells.     

Perspectives on Potential Fatty Acid Modulations of Motility Associated Human Sperm Ion Channels

Human spermatozoan ion channels are specifically distributed in the spermatozoan membrane, contribute to sperm motility, and are associated with male reproductive abnormalities. Calcium, potassium, protons, sodium, and chloride are the main ions that are regulated across this membrane, and their intracellular concentrations are crucial for sperm motility. Fatty acids (FAs) affect sperm quality parameters, reproductive pathologies, male fertility, and regulate ion channel functions in other cells. However, to date the literature is insufficient to draw any conclusions regarding the effects of FAs on human spermatozoan ion channels. Here, we aimed to discern the possible effects of FAs on spermatozoan ion channels and direct guidance for future research. After investigating the effects of FAs on characteristics related to human spermatozoan motility, reproductive pathologies, and the modulation of similar ion channels in other cells by FAs, we extrapolated polyunsaturated FAs (PUFAs) to have the highest potency in modulating sperm ion channels to increase sperm motility. Of the PUFAs, the ω-3 unsaturated fatty acids have the greatest effect. We speculate that saturated and monounsaturated FAs will have little to no effect on sperm ion channel activity, though the possible effects could be opposite to those of the PUFAs, considering the differences between FA structure and behavior.