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Results for “Membrane Transport Modulators”

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PubMed1981

Cation transport and growth regulation in neuroblastoma cells. Modulations of K+ transport and electrical membrane properties during the cell cycle.

Cation transport and membrane potential were studied during the cell cycle of neuroblastoma cells (clone Neuro-2A) to investigate the role of these parameters in growth regulation. The cells were synchronized by selective detachment of mitotic cells. The membrane potential and intracellular K+ activity were measured with conventional and K+-selective microelectrodes respectively. Both the membrane potential and K+ activity were high in mitosis, decreased to half maximal in G1 phase, and rose again during S phase. K+ efflux across the plasma membrane was studied with 42K+ as a radioactive tracer using a washing method for cells grown in monolayer and a continuous efflux method for mitotic cells in suspension. The intracellular K+ content and unidirectional K+ efflux rate obtained from these measurements showed modulations during the cell cycle similar to those of the membrane potential. Using equations of electrodiffusion theory the membrane permeabilities to K+ and Na+ were calculated. These permeabilities were high in mitosis, decreased rapidly in G1 phase and increased during S phase, followed by a transient decrease in G2 phase. A rapid increase was observed between G2 phase and the next mitosis. A similar pattern was obtained for the K+ conductance. K+ resistance changes during the cell cycle were similar to changes in the specific membrane resistance, measured by microelectrodes, except for the early cell cycle phases (mitosis and G1). These studies clearly demonstrate large modulations of the passive membrane permeability properties during the cell cycle. These modulations can be correlated with physicochemical membrane variations during the cell cycle, such as membrane fluidity and lateral mobility of lipids.

Animals↗

PubMed2006

Ion-channel regulation of chondrocyte matrix synthesis in 3D culture under static and dynamic compression.

Inhibition of various ion channels alters chondrocyte mechanotransduction in monolayer, but the mechanisms involved in chondrocyte mechanotransduction in three- dimensional culture remain unclear. The objective of this study was to investigate the effects of inhibiting putative ion-channel influenced mechanotransduction mechanisms on the chondrocyte responses to static and dynamic compression in three-dimensional culture. Bovine articular cartilage explants were used to investigate the dose-dependent inhibition and recovery of protein and sulfated glycosaminoglycan (sGAG) syntheses by four ion-channel inhibitors: 4-Aminopyridine (4AP), a K(+) channel blocker; Nifedipine (Nf), a Ca(2+) channel blocker; Gadolinium (Gd), a stretch-activated channel blocker; and Thapsigargin (Tg), which releases intracellular Ca(2+) stores by inhibiting ATP-dependent Ca(2+) pumps. Chondrocyte-seeded agarose gels were used to examine the influence of 20 h of static and dynamic loading in the presence of each of the inhibitors. Overall, treatment with the ion-channel inhibitors had a greater effect on sGAG synthesis, with the exception of Nf, which more substantially affected protein synthesis. Treatment with Tg significantly impaired both overall protein and sGAG synthesis, with a drastic reduction in sGAG synthesis. The inhibitors differentially influenced the responses to mechanical stimuli. Dynamic compression significantly upregulated protein synthesis but did not significantly affect sGAG synthesis with Nf or Tg treatment. Dynamic compression significantly upregulated both protein and sGAG synthesis rates with Gd treatment. There was no significant stimulation of either protein or sGAG synthesis by dynamic compression with 4AP treatment. Interruption of many ion-channel signaling mechanisms affected sGAG synthesis, suggesting a complicated, multi-pathway signaling process. Also, Ca(2+) signaling may be critical for the transduction of mechanical stimulus in regulating sGAG synthesis. This modulation potentially occurs through direct interactions with the extracellular matrix.

Animals↗

PubMed2006

The functions and structure of ABC transporters: implications for the design of new inhibitors of Pgp and MRP1 to control multidrug resistance (MDR).

Multidrug resistance (MDR) is a kind of acquired resistance of microorganisms and cancer cells to chemotherapic drugs that are characterized by different chemical structure and different mechanism of action. Classic MDR is the consequence of the over-expression of a variety of proteins that extrude the chemotherapic from the cell, lowering its concentration below the effective one. The ABC (ATP Binding Cassette) is a ubiquitous and important family of such transporter proteins. Members of this super family are present in mammals as well as in prokaryotic organisms and use ATP as the energy source to activate the extrusion process. P-glycoprotein (Pgp) and Multidrug Resistance Proteins (MRP1 and sister proteins) are the most important and widely studied members of ABC super family. Our knowledge about the structures and functions of transporter proteins has definitely improved in recent years, following the resolution of the structure of bacterial pumps which opened the way to the building of homology models for the more complex Pgp and MRP. It can be anticipated that these results will have a strong impact on the design of more potent and safer MDR reverters. A huge number of small molecules, many of natural origin, are able to reverse multidrug resistance by inhibiting the functions of Pgp, MRP1 and sister proteins and their action has been considered a possible way to reverse MDR. However, while a few compounds have reached clinical trials, none of them has, so far, been cleared for therapeutic use. Two main reasons are at the base of this difficulty: i) MDR is a complex phenomenon that may arise from several different biochemical mechanisms, with the consequence that inhibition of transporter proteins may be insufficient to reverse it; ii) the physiological role of Pgp and sister proteins requires more potent modulators with proper selectivity and pharmacokinetic in order to avoid unwanted side effects. This paper first reviews the most recent discoveries on the structures and functions of the ABC super family, in particular Pgp and MRP. Then, the medicinal chemistry of MDR reverters, in light of these findings, is discussed and the molecules that are presently in development are reviewed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Partial structures of ketoconazole as modulators of the large conductance calcium-activated potassium channel (BK(Ca)).

A series of partial structures of ketoconazole has been synthesized and tested for activity on the large conductance calcium-activated potassium channel (BK) in bovine smooth muscle cells. This has provided openers and blockers of the channel. The results suggest that the phenyl and phenoxy moieties are important for interaction with BK, whereas the imidazole group is unimportant. The properties of the phenoxy moiety seem to determine whether the compounds act to open or block the channel.

Animals↗

PubMed2006

Pathological circumstances impair the ability of "dark" neurons to undergo spontaneous recovery.

The effects of dehydrating drugs (furosemide, mannitol and glycerine), potassium channel modulators (tetraethylammonium chloride, 5-hydroxydecanoic acid Na salt, minoxidil and pinacidil), sodium channel modulators (veratridine, brevetoxin-9, 5-(N,N-dimethyl)amiloride and benzamil-HCl) and mitochondrial enzyme inhibitors (3-nitropropionic acid, 2,4-dinitrophenol and chloramphenicol) on the fate of electrically produced "dark" hippocampal dentate granule neurons were investigated. All but one (chloramphenicol) of these bioactive reagents substantially retarded the recovery and increased the death rate of such "dark" neurons. As concerns the dehydrating drugs and ion channel modulators, these effects are considered to be consequences of the fact that relatively large volumes (more than half of the original cell volume) of cytoplasmic fluid (water molecules, inorganic ions and metabolites) leave the affected cells through passive pores within a few minutes. The effects of the mitochondrial enzyme inhibitors appear to indicate that restoration of the original cell volume (recovery) demands metabolic (enzyme-mediated) energy. All these features support our previous assumption that the exogenous circumstances existing acutely after the formation of "dark" neurons in neurological diseases decide whether they will recover or die.

Animals↗

PubMed1994

Renal brush border membrane lipid composition in Basenji dogs with spontaneous idiopathic Fanconi syndrome.

To comprehend the renal defect underlying idiopathic Fanconi syndrome in the Basenji dog, we have focused on delineating the lipid profiles of renal brush border membranes isolated from affected and normal Basenji dogs to establish any physical or compositional changes underlying previously observed transport and membrane-fluidity changes. The lipid composition was studied with respect to total lipid, cholesterol, and phospholipid content, cholesterol to phospholipid ratio, distribution of the major phospholipid classes, and fatty acid composition. Total phospholipid of the isolated renal brush border membranes from Fanconi syndrome dogs analyzed by 31P nuclear magnetic resonance showed no difference compared with that of normal dogs. Examination of total fatty acids in both membranes using gas-liquid chromatography analysis of fatty acid methyl esters showed no difference in the mole percents of the major fatty acids. Our data suggest that changes in bulk membrane fluidity of the Fanconi syndrome dog renal brush border as measured by 1,6-diphenyl-1,3,5-hexatriene cannot be attributed to phospholipid and fatty acid compositional change. In the membranes isolated from affected dog kidney, the cholesterol content determined by gas-liquid chromatography analysis was 66 mol% higher than in membranes isolated from normal dog kidney. This correlates with the higher cholesterol to phospholipid molar ratio of 0.82 +/- 0.08 in the affected animal as compared with 0.58 +/- 0.04 in the normal. Cholesterol content and its microdomain in the membrane bilayer may be important in modulating transport functions. Increased membrane cholesterol content may affect the conformational motility of membrane transport proteins and thus affect their function.

Animals↗

PubMed2006

Pharmacological strategies for overcoming multidrug resistance.

Multidrug resistance (MDR) is a major obstacle to the effective treatment of cancer. One of the underlying mechanisms of MDR is cellular overproduction of P-glycoprotein (P-gp) which acts as an efflux pump for various anticancer drugs. P-gp is encoded by the MDR1 gene and its overexpression in cancer cells has become a therapeutic target for circumventing multidrug resistance. A potential strategy is to co-administer efflux pump inhibitors, although such reversal agents might actually increase the side effects of chemotherapy by blocking physiological anticancer drug efflux from normal cells. Although many efforts to overcome MDR have been made using first and second generation reversal agents comprising drugs already in current clinical use for other indications (e.g. verapamil, cyclosporine A, quinidine) or analogues of the first-generation drugs (e.g. dexverapamil, valspodar, cinchonine), few significant advances have been made. Clinical trials with third generation modulators (e.g. biricodar, zosuquidar, and laniquidar) specifically developed for MDR reversal are ongoing. The results however are not encouraging and it may be that the perfect reverser does not exist. Other approaches to multidrug resistance reversal have also been considered: encapsulation of anthracyclines in liposomes or other carriers which deliver these drugs selectively to tumor tissues, the use of P-gp targeted antibodies such as UIC2 or the use of antisense strategies targeting the MDR1 messenger RNA. More recently, the development of transcriptional regulators appears promising. Also anticancer drugs that belong structurally to classes of drugs extruded from cells by P-gp but that are not substrates of this drug transporter may act as potent inhibitors of MDR tumors (e.g. epothilones, second generation taxanes). Taking advantage of MDR has also been studied. Bone marrow suppression, one of the major side effects of cancer chemotherapy, can compromise the potential of curative and palliative chemotherapy. It is conceivable that drug resistance gene transfer into bone marrow stem cells may be able to reduce or abolish chemotherapy-induced myelosuppression and facilitate the use of high dose chemotherapy. Clinical trials of retroviral vectors containing drug resistance genes have established that the approach is safe and are now being designed to address the therapeutically relevant issues.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Novel 384-well population patch clamp electrophysiology assays for Ca2+-activated K+ channels.

Planar array electrophysiology techniques were applied to assays for modulators of recombinant hIK and hSK3 Ca2+-activated K+ channels. In CHO-hIK-expressing cells, under asymmetric K+ gradients, small-molecule channel activators evoked time- and voltage-independent currents characteristic of those previously described by classical patch clamp electrophysiology methods. In single-hole (cell) experiments, the large cell-to-cell heterogeneity in channel expression rendered it difficult to generate activator concentration-response curves. However, in population patch clamp mode, in which signals are averaged from up to 64 cells, well-to-well variation was substantially reduced such that concentration-response curves could be easily constructed. The absolute EC50 values and rank order of potency for a range of activators, including 1-EBIO and DC-EBIO, corresponded well with conventional patch clamp data. Activator responses of hIK and hSK3 channels could be fully and specifically blocked by the selective inhibitors TRAM-34 and apamin, with IC50 values of 0.31 microM and 3 nM, respectively. To demonstrate assay precision and robustness, a test set of 704 compounds was screened in a 384-well format of the hIK assay. All plates had Z' values greater than 0.6, and the statistical cutoff for activity was 8%. Eleven hits (1.6%) were identified from this set, in addition to the randomly spiked wells with known activators. Overall, our findings demonstrate that population patch clamp is a powerful and enabling method for screening Ca2+-activated K+ channels and provides significant advantages over single-cell electrophysiology (IonWorks(HT)) and other previously published approaches. Moreover, this work demonstrates for the 1st time the utility of population patch clamp for ion channel activator assays and for non-voltage-gated ion channels.

Animals↗

PubMed1985

The DC-ERG as a highly sensitive measure of effects of prostaglandins.

A few microliters of a prostaglandin preparation (PGE2 or PGF2 alpha) were injected via the ora serrata into the posterior vitreous of one of the eyes in albino rabbits. The fellow eye received an equal volume of saline intravitreally and served as control. The DC electroretinogram (ERG) and the standing potential of the eye (SP) were recorded directly with corneal contact lenses, very stable calomel electrodes, and under very constant anesthesia. The b- and c-wave amplitudes increased in response to 0.1 and 1.0 microgram of PGE2 and PGF2 alpha, respectively. At medium doses there was an increase in the b- and c-wave amplitudes followed by a long-lasting reduction. At very high, nonphysiological doses of PGE2, b- and c-wave amplitudes decreased as compared with the control eye. Prostaglandins modify inflammatory reactions, influence ion transport across membranes, modulate synaptic transmission, and regulate blood flow to various organs. Effects of extremely low doses on the retina and pigment epithelium might indicate a transmitter-like nature of prostaglandins. The present experimental model might be of use in studies of inflammatory eye disease, prostaglandin inhibitors, and characteristics of the pigment epithelial membranes.

Animals↗

PubMed2006

Diversity of Cl(-) channels.

Cl(-) channels are widely found anion pores that are regulated by a variety of signals and that play various roles. On the basis of molecular biologic findings, ligand-gated Cl(-) channels in synapses, cystic fibrosis transmembrane conductors (CFTRs) and ClC channel types have been established, followed by bestrophin and possibly by tweety, which encode Ca(2+)-activated Cl(-) channels. The ClC family has been shown to possess a variety of functions, including stabilization of membrane potential, excitation, cell-volume regulation, fluid transport, protein degradation in endosomal vesicles and possibly cell growth. The molecular structure of Cl(-) channel types varies from 1 to 12 transmembrane segments. By means of computer-based prediction, functional Cl(-) channels have been synthesized artificially, revealing that many possible ion pores are hidden in channel, transporter or unidentified hydrophobic membrane proteins. Thus, novel Cl(-)-conducting pores may be occasionally discovered, and evidence from molecular biologic studies will clarify their physiologic and pathophysiologic roles.

Animals↗

PubMed2006

RSD1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agents.

OBJECTIVE: RSD1235 is a novel antiarrhythmic drug with atria-selective electrophysiological actions on Na(+) and K(+) currents. The mechanism for its protection of ventricular repolarization was assessed by its action on Purkinje fibers, and by block of late sodium current active during repolarization. Further, RSD1235's ability to reverse the pro-arrhythmic actions of the class III agents dofetilide and clofilium was assessed in isolated Purkinje fibers and an in vivo model of torsades de pointes (TdP). METHODS: Action potential and early after-depolarization (EAD) recordings were made from in situ and isolated rabbit Purkinje fibers at 37 degrees C using floating sharp microelectrodes; late I(Na) was recorded using a whole-cell patch clamp technique of Nav1.5 expressed in HEK cells at 22 degrees C; In vivo, anesthetized methoxamine-sensitized rabbits were used to test the ability of RSD1235 to suppress clofilium-induced TdP. RESULTS: RSD1235 (0.5-30 microM) had minor dose-dependent effects on action potential duration (APD) at 50% and 90% repolarization in Purkinje fibers, but pre-treatment significantly attenuated the APD-prolonging effects of dofetilide (300 nM). EADs induced by 300 nM dofetilide were terminated by 30 microM RSD1235 in all experiments (n=7). RSD1235 blocked a late component of Na current (I(Na)), which can produce inward currents contributing to EAD formation. RSD1235 pre-treatment (1 micromol/kg/min) or acute infusions prevented/terminated TdP induced by clofilium in 8 of 9 rabbits, and reduced the duration of TdP episodes from 71 +/- 23 s in control to 17 +/- 7 and 14 +/- 14 s at infusion rates of 0.3 and 1.0 micromol/kg/min, respectively (n = 9, p < 0.001). CONCLUSION: RSD1235 itself has minor actions on repolarization in Purkinje fibers, but can reverse the AP-prolonging actions of class III agents and terminate arrhythmias in a model of TdP. We suggest that these protective actions of RSD1235 may result, at least in part, from its ability to inhibit late I(Na) during action potential repolarization.

Action Potentials↗

PubMed2004

Role of the betaine/GABA transporter (BGT-1/GAT2) for the control of epilepsy.

Inactivation of gamma-aminobutric acid (GABA) as a neurotransmitter is mediated by diffusion in the synaptic cleft followed by binding to transporter sites and translocation into the intracellular compartment. The GABA transporters of which four subtypes have been cloned (GAT1-4) are distributed at presynaptic nerve endings as well as extrasynaptically on astrocytic and neuronal elements. This anatomical arrangement of the transporters appears to be of critical functional importance for the maintenance of GABAergic neurotransmission. Pharmacological characterization of the GABA transporters using a large number of GABA analogs having restricted conformation and lipophilic character has been of instrumental importance for elucidation of the functional importance of the different transporters. One such analog EF1502 (N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-hydroxy-4-methylamino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol) has been shown to selectively inhibit GAT1 (GABA transporter 1) and GAT2/BGT-1 (betaine/GABA transporter). Moreover, this GABA analog exhibits an unusually high efficiency as an anticonvulsant suggesting a novel role of the betaine/GABA transporter in epileptic seizure control. It is hypothesized that extrasynaptic actions of GABA may be involved in this phenomenon.

Animals↗

PubMed2005

A mathematical model of ion movements in grey matter during a stroke.

The development of cytotoxic oedema during a stroke consists in cell swelling and shrinking of the extracellular space. This phenomenon is triggered by ion movements through voltage-gated channels, exchangers and pumps. During ischaemia, sodium, calcium and chloride enter the neurons whereas potassium and glutamate are expelled out of the cells. A mathematical model is proposed to represent the long-term dynamics of membrane potentials, cell volumes and ionic concentrations in intracellular and extracellular spaces during a stroke and to study the influence of each ionic current on cell swelling. The model relies on electrophysiological mechanisms and takes into account the behaviour of two types of cells: neurons and also astrocytes known to play a key role in the excitotoxic process in grey matter. The results obtained when a severe or a moderate ischaemia is simulated are consistent with those observed in the in vitro and in vivo experiments. As this model appears to be robust, it is used to perform illustrative simulations aimed at studying the effect of some channel blockers on cell swelling. This approach may help to explore new therapeutic strategies in order to reduce stroke damage.

Astrocytes↗

PubMed2005

The 5-HT- and FMRFa-activated signaling pathways interact at the level of the Erk MAPK cascade: potential inhibitory constraints on memory formation.

The sensorimotor synapse of Aplysia exhibits long-term facilitation (LTF) and long-term depression (LTD) elicited by the neuromodulator serotonin (5-HT) and the peptide Phe-Met-Arg-Phe-NH(2), respectively. 5-HT-induced LTF engages extracellular-regulated kinase (Erk) and CREB1, whereas FMRFa-induced LTD engages p38 MAPK (mitogen-activated protein kinase) and CREB2. The interaction of the 5-HT and FMRFa pathways was recently investigated in Aplysia at the level of gene expression. However, little is known about crosstalk of these pathways at the level of the second messenger cascades. We investigated the potential interaction of the 5-HT and FMRFa pathways at the level of the Erk cascade. We found that FMRFa inhibited basal Erk activity through p38 MAPK. FMRFa also inhibited 5-HT-induced phosphorylation of Erk and nuclear accumulation of phospho-ERK, suggesting that FMRFa may place inhibitory constraints on memory formation through regulation of the Erk MAPK cascade.

Animals↗

PubMed2006

Sensitivity of pressor responses to central hypertonic saline is greatly enhanced even in pre-hypertensive spontaneously hypertensive rats.

It has been suggested that intracerebroventricular injection of hypertonic saline mimics the effects of a high salt diet in spontaneously hypertensive rats (SHR), a genetic model of hypertension. Intracerebroventricular injection of hypertonic saline produces an increase in blood pressure and the pressor response to hypertonic saline is enhanced in adult hypertensive SHR. In this study, we examined whether the intracerebroventricular hypertonic saline-induced pressor response is enhanced even in pre-hypertensive SHR. The basal mean blood pressure was almost the same in 4-week-old SHR and age-matched Wistar Kyoto rats (WKY), whereas it was greater in 15-16-week-old SHR than in age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 230 mM NaCl) produced an increase in blood pressure in both 4-week-old and 15-16-week-old SHR, whereas it did not affect blood pressure in both age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 260 mM NaCl) produced an increase in blood pressure in all rats but the pressor response was greater in both 4-week-old and 15-16-week-old SHR than in respective age-matched WKY. Intracerebroventricular injection of Phe-Met-Arg-Phe amide (FMRF), an FMRF-inducible sodium channel activator, produced an increase in blood pressure in all rats but the pressor response was greater in SHR than in WKY at both ages. These findings indicate that the sensitivities of pressor responses to intracerebroventricular hypertonic saline and FMRF are enhanced not only in hypertensive but also in pre-hypertensive SHR.

Animals↗

PubMed2006

Isolation and characterization of Jingzhaotoxin-V, a novel neurotoxin from the venom of the spider Chilobrachys jingzhao.

Jingzhaotoxin-V (JZTX-V), a 29-residue polypeptide, is derived from the venom of the spider Chilobrachys jingzhao. Its cDNA determined by rapid amplification of 3' and 5'-cDNA ends encoded an 83-residue precursor with a pro-region of 16 residues. JZTX-V inhibits tetrodotoxin-resistant and tetrodotoxin-sensitive sodium currents in rat dorsal root ganglion neurons with IC50 values of 27.6 and 30.2 nM, respectively. Moreover, the toxin exhibits high affinity to the resting closed states of the channels. JZTX-V also inhibits Kv4.2 potassium currents expressed in Xenpus Laevis oocytes (IC50=604.2 nM), but has no effects on outward delay-rectified potassium channels expressed in Xenopus laevis oocytes. JZTX-V alters the gating properties of sodium channels by shifting the activation curves to the depolarizing direction and the inactivation curves to the hyperpolarizing direction. Small unilamellar vesicles binding assays show that the partitioning of JZTX-V into lipid bilayer requires negatively charged phospholipids. The phospholipid membrane binding activity of JZTX-V is also verified using intrinsic tryptophan fluorescence analysis as well as acrylamide-quenching assays. Importantly, human multiple sodium channel subtypes are attractive targets for treatment of pain, highlighting the importance of JZTX-V as potential lead for drug development.

Acrylamide↗

PubMed2003

Intravesicular glucose modulates magnesium2+ transport in liver plasma membrane from streptozotocin-treated rats.

Plasma membrane vesicles purified from livers of 4-week-old streptozotocin-injected diabetic rats present an increased basal and cation-stimulated magnesium (Mg)2+ transport as compared with vesicles purified from age-matched nondiabetic animals. Furthermore, diabetic basolateral membranes are unable to accumulate extravesicular Mg2+ in exchange for intravesicular sodium (Na)+. Loading diabetic vesicles with varying concentrations of D-glucose, in addition to Mg2+, renormalizes basal and Na+- or calcium (Ca)2+-induced Mg2+ extrusion in a dose-dependent manner, but does not restore Na+/Mg2+ exchanger reversibility. A similar effect on Mg2+ extrusion is observed when D-glucose is replaced with 2-deoxy-glucose, amylopectin, or glycogen. The loading with 3-methyl-O-glucose or L-glucose, instead, affects basal and Na+-dependent Mg2+ extrusion, but not Ca2+-dependent Mg2+ fluxes. In contrast, loading the vesicles with hexoses other than glucose or varying extravesicular glucose concentration from 5 to 20 mmol/L does not modify basal or cation-stimulated Mg2+ fluxes. Taken together, these data indicate that basal and cation-stimulated Mg2+ transport across the hepatocyte plasma membrane is altered under diabetic conditions as a result of a decrease in intravesicular (intracellular) glucose.

Adenosine Triphosphate↗

PubMed2001

Single guard cell recordings in intact plants: light-induced hyperpolarization of the plasma membrane.

Guard cells are electrically isolated from other plant cells and therefore offer the unique possibility to conduct current- and voltage-clamp recordings on single cells in an intact plant. Guard cells in their natural environment were impaled with double-barreled electrodes and found to exhibit three physiological states. A minority of cells were classified as far-depolarized cells. These cells exhibited positive membrane potentials and were dominated by the activity of voltage-dependent anion channels. All other cells displayed both outward and inward rectifying K+-channel activity. These cells were either depolarized or hyperpolarized, with average membrane potentials of -41 mV (SD 16) and -112 mV (SD 19), respectively. Depolarized guard cells extrude K+ through outward rectifying channels, while K+ is taken up via inward rectifying channels in hyperpolarized cells. Upon a light/dark transition, guard cells that were hyperpolarized in the light switched to the depolarized state. The depolarization was accompanied by a 35 pA decrease in pump current and an increase in the conductance of inward rectifying channels. Both an increase in pump current and a decrease in the conductance of the inward rectifier were triggered by blue light, while red light was ineffective. From these studies we conclude that light modulates plasma membrane transport through large membrane potential changes, reversing the K+-efflux via outward rectifying channels to a K+-influx via inward rectifying channels.

Calcium Channels↗