Evolution and expression of class III peroxidases

Class III peroxidases are members of a large multigenic family, only detected in the plant kingdom and absent from green algae sensu stricto (chlorophyte algae or Chlorophyta). Their evolution is thought to be related to the emergence of the land plants. However class III peroxidases are present in a lower copy number in some basal Streptophytes (Charapyceae), which predate land colonization. Gene structures are variable among organisms and within species with respect to the number of introns, but their positions are highly conserved. Their high copy number, as well as their conservation could be related to plant complexity and adaptation to increasing stresses. No specific function has been assigned to respective isoforms, but in large multigenic families, particular structure-function relations can be expected. Plant peroxidase sequences contain highly conserved residues and motifs, variable domains surrounded by conserved residues and present a low identity level among their promoter regions, further suggesting the existence of sub-functionalization of the different isoforms.     

Cloning and functional expression of novel N-type Ca(2+) channel variants

Voltage-dependent Ca(2+) channels are structurally and functionally diverse. As Ca(2+) currents recorded from embryonic chick dorsal root ganglion (DRG) neurons differ significantly from their mammalian counterparts, information on the primary sequence of the chick channels will help define the structural underpinnings of Ca(2+) channel function. Here, we report the cloning and functional expression of full-length Ca(2+) channel alpha(1B) subunit cDNAs derived from chick DRGs. Two variable regions (A and B) have been identified in the cytoplasmic linker between repeats I and II; a third (C) in the carboxyl terminus extends the open reading frame by 525 nucleotides. The A and C inserts are absent, and the B insert is present in all other class B clones reported to date. The unique shorter channels appear to predominate in DRG neurons. Results represent a requisite first step in defining the structural elements that underlie variations in function and modulation of Ca(2+) channels.     

Calcium-permeable channels in plant cells

Calcium signal transduction is a central mechanism by which plants sense and respond to endogenous and environmental stimuli. Cytosolic Ca(2+) elevation is achieved via two cellular pathways, Ca(2+) influx through Ca(2+) channels in the plasma membrane and Ca(2+) release from intracellular Ca(2+) stores. Because of the significance of Ca(2+) channels in cellular signaling, interaction with the environment and developmental processes in plants, a great deal of effort has been invested in recent years with regard to these important membrane proteins. Because of limited space, in this review we focus on recent findings giving insight into both the molecular identity and physiological function of channels that have been suggested to be responsible for the elevation in cytosolic Ca(2+) level, including cyclic nucleotide gated channels, glutamate receptor homologs, two-pore channels and mechanosensitive Ca(2+) -permeable channels. We provide an overview of the regulation of these Ca(2+) channels and their physiological roles and discuss remaining questions.     

Genes for calcium-permeable channels in the plasma membrane of plant root cells

In plant cells, Ca(2+) is required for both structural and biophysical roles. In addition, changes in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) orchestrate responses to developmental and environmental signals. In many instances, [Ca(2+)](cyt) is increased by Ca(2+) influx across the plasma membrane through ion channels. Although the electrophysiological and biochemical characteristics of Ca(2+)-permeable channels in the plasma membrane of plant cells are well known, genes encoding putative Ca(2+)-permeable channels have only recently been identified. By comparing the tissue expression patterns and electrophysiology of Ca(2+)-permeable channels in the plasma membrane of root cells with those of genes encoding candidate plasma membrane Ca(2+) channels, the genetic counterparts of specific Ca(2+)-permeable channels can be deduced. Sequence homologies and the physiology of transgenic antisense plants suggest that the Arabidopsis AtTPC1 gene encodes a depolarisation-activated Ca(2+) channel. Members of the annexin gene family are likely to encode hyperpolarisation-activated Ca(2+) channels, based on their corresponding occurrence in secretory or elongating root cells, their inhibition by La(3+) and nifedipine, and their increased activity as [Ca(2+)](cyt) is raised. Based on their electrophysiology and tissue expression patterns, AtSKOR encodes a depolarisation-activated outward-rectifying (Ca(2+)-permeable) K(+) channel (KORC) in stelar cells and AtGORK is likely to encode a KORC in the plasma membrane of other Arabidopsis root cells. Two candidate gene families, of cyclic-nucleotide gated channels (CNGC) and ionotropic glutamate receptor (GLR) homologues, are proposed as the genetic correlates of voltage-independent cation (VIC) channels.     

C4 characteristics of photosynthesis in the C3 alga Hydrodictyon africanum

Abstract Results obtained with Hydrodictyon africanum, and data from the literature, show that most green algae of the chlorophyte type (e.g. Chlorella, Chlamydomonas, Hydrodictyon) differ in their photosynthetic C fixation characteristics from most green algae of the charophyte type (e.g. Spirogyra, Chara) and from C₃ higher plants. The chlorophyte algae fix inorganic carbon by the photosynthetic carbon reduction cycle pathway, but have a low CO₂ compensation point in 250 μM O₂, a low inhibition of CO₂ fixation from 10 μM CO₂/250 μM O₂ when compared with 10 μM CO₂/zero O₂, and a low half-saturation constant for CO₂. These three characteristics are different from those of charophytes and C₃ higher plants, and resemble those of C₄ higher plants. It is suggested that these characteristics of chlorophyte algae are the result of a ‘CO₂ concentrating mechanism’ which increases the CO₂/O₂ ratio at the site of ribulose bisphosphate carboxylase-oxygenase action in a similar way to that achieved by the C₄?C₃ acid cycle in C₄ plants. In the chlorophyte algae, however, CO₂ concentration probably involves active HCO₃^? transport at the inner membrane of the chloroplast envelope. Active HCO₃^? transport can occur at the plasmalemma of charophyte algae and submerged aquatic higher plants as well as chlorophyte algae, so it is unlikely to explain the differences between the two groups of aquatic green plants. Differences in the properties of ribulose bisphosphate carboxylase-oxygenase, and differences in CO₂ production in the light, also seem inadequate to account for the different photosynthetic characteristics. The chlorophyte type of ‘C0₂ concentrating mechanism’ appears to be common in other classes of eukaryotic algae, and in cyanophytes. Some of the ‘advanced’ members of these eukaryotic algal classes (including the chlorophytes) may lack the mechanism, while some ‘primitive’ charophytes may retain the mechanism which their ancestors presumably possessed.     

A Ca(2+)- and voltage-modulated flagellar ion channel is a component of the mechanoshock response in the unicellular green alga Spermatozopsis similis

In flagellate green algae, behavioral responses to photo- and mechanoshock are induced by different external stimuli within 10-15 ms. In the accompanying changes in flagella beat, Ca(2+) has important regulatory roles. Although the axonemal Ca(2+) responsive elements are well characterized, analyses of flagellar channels involved in Ca(2+) signalling as well as other ion channels at the single-channel level were not yet conducted in green algae. To gain a further understanding of these important signaling elements in movement responses, intact flagella of Spermatozopsis similis were isolated and characterized and the solubilized flagellar membrane proteins were reconstituted into liposomes. We observed three types of channel activity, two of which were weakly anion and cation-selective and in the high-conductance regime typical for porin-like solute channels. The dominating channel activity was a voltage dependent, rectifying, low conductance (Lambda=80 pS in 50 mM KCl) cation-selective channel modulated by, and highly permeable to, Ca(2+) ions (SFC1: Spermatozopsis flagellar cation channel 1). Depolarizations necessary to activate SFC1 probably only occur in vivo during avoidance reactions of this alga. Ca(2+)-activation of SFC1 points to a direct link to Ca(2+)-mediated signaling pathway(s) in the flagella. Both the response to mechanoshock and SFC1 activity were inhibited by Gd(3+) and Ba(2+), thus supporting our assumption that SFC1 represents a major flagellar ion channel involved in this green algal avoidance reaction.     

Calcium channels are involved in calcium oxalate crystal formation in specialized cells of Pistia stratiotes L

BACKGROUND AND AIMS: Pistia stratiotes produces large amounts of calcium (Ca) oxalate crystals in specialized cells called crystal idioblasts. The potential involvement of Ca(2+) channels in Ca oxalate crystal formation by crystal idioblasts was investigated. METHODS: Anatomical, ultrastructural and physiological analyses were used on plants, fresh or fixed tissues, or protoplasts. Ca(2+) uptake by protoplasts was measured with (45)Ca(2+), and the effect of Ca(2+) channel blockers studied in intact plants. Labelled Ca(2+) channel blockers and a channel protein antibody were used to determine if Ca(2+) channels were associated with crystal idioblasts. KEY RESULTS: (45)Ca(2+) uptake was more than two orders of magnitude greater for crystal idioblast protoplasts than mesophyll protoplasts, and idioblast number increased when medium Ca was increased. Plants grown on media containing 1-50 microM of the Ca(2+) channel blockers, isradipine, nifedipine or fluspirilene, showed almost complete inhibition of crystal formation. When fresh tissue sections were treated with the fluorescent dihydropyridine-type Ca(2+) channel blocker, DM-Bodipy-DHP, crystal idioblasts were intensely labelled compared with surrounding mesophyll, and the label appeared to be associated with the plasma membrane and the endoplasmic reticulum, which is shown to be abundant in idioblasts. An antibody to a mammalian Ca(2+) channel alpha1 subunit recognized a single band in a microsomal protein fraction but not soluble protein fraction on western blots, and it selectively and heavily labelled developing crystal idioblasts in tissue sections. CONCLUSIONS: The results demonstrate that Ca oxalate crystal idioblasts are enriched, relative to mesophyll cells, in dihydropyridine-type Ca(2+) channels and that the activity of these channels is important to transport and accumulation of Ca(2+) required for crystal formation.     

A close association of RyRs with highly dense clusters of Ca2+-activated Cl- channels underlies the activation of STICs by Ca2+ sparks in mouse airway smooth muscle

Ca(2+) sparks are highly localized, transient releases of Ca(2+) from sarcoplasmic reticulum through ryanodine receptors (RyRs). In smooth muscle, Ca(2+) sparks trigger spontaneous transient outward currents (STOCs) by opening nearby clusters of large-conductance Ca(2+)-activated K(+) channels, and also gate Ca(2+)-activated Cl(-) (Cl((Ca))) channels to induce spontaneous transient inward currents (STICs). While the molecular mechanisms underlying the activation of STOCs by Ca(2+) sparks is well understood, little information is available on how Ca(2+) sparks activate STICs. In the present study, we investigated the spatial organization of RyRs and Cl((Ca)) channels in spark sites in airway myocytes from mouse. Ca(2+) sparks and STICs were simultaneously recorded, respectively, with high-speed, widefield digital microscopy and whole-cell patch-clamp. An image-based approach was applied to measure the Ca(2+) current underlying a Ca(2+) spark (I(Ca(spark))), with an appropriate correction for endogenous fixed Ca(2+) buffer, which was characterized by flash photolysis of NPEGTA. We found that I(Ca(spark)) rises to a peak in 9 ms and decays with a single exponential with a time constant of 12 ms, suggesting that Ca(2+) sparks result from the nonsimultaneous opening and closure of multiple RyRs. The onset of the STIC lags the onset of the I(Ca(spark)) by less than 3 ms, and its rising phase matches the duration of the I(Ca(spark)). We further determined that Cl((Ca)) channels on average are exposed to a [Ca(2+)] of 2.4 microM or greater during Ca(2+) sparks. The area of the plasma membrane reaching this level is <600 nm in radius, as revealed by the spatiotemporal profile of [Ca(2+)] produced by a reaction-diffusion simulation with measured I(Ca(spark)). Finally we estimated that the number of Cl((Ca)) channels localized in Ca(2+) spark sites could account for all the Cl((Ca)) channels in the entire cell. Taken together these results lead us to propose a model in which RyRs and Cl((Ca)) channels in Ca(2+) spark sites localize near to each other, and, moreover, Cl((Ca)) channels concentrate in an area with a radius of approximately 600 nm, where their density reaches as high as 300 channels/microm(2). This model reveals that Cl((Ca)) channels are tightly controlled by Ca(2+) sparks via local Ca(2+) signaling.     

Atypical Ca2+ currents in chromaffin cells from SHR and WKY rat strains result from the deficient expression of a splice variant of the α1D Ca2+ channel

Ca(2+) currents (I(Ca)) recorded from adrenal chromaffin cells (CCs) of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats are similar to one another, but different from those recorded in other rodent species. I(Ca) in WKY/SHR CCs comprises an early, transient (I(Ca(e))) and a late, sustained component (I(Ca(s))). In Wistar CCs, I(Ca(e)) is absent, and I(Ca(s)) is of greater amplitude. Activation and steady-state inactivation of I(Ca(e)) and I(Ca(s)) in WKY/SHR CCs suggest the recruitment of at least two populations of Ca(2+) channels with different voltage dependence and kinetics. In WKY/SHR CCs, I(Ca(e)) is inhibited by nifedipine, enhanced by BAY K 8644, is not blocked by the mibefradil analog NNC 55-0396, and displays Ca(2+)-dependent inactivation and fast deactivation kinetics, suggesting that it results from the opening of L-type rather than T-type Ca(2+) channels. I(Ca(e)) properties suggest that it originates from the opening of Ca(2+) channels formed with the short splice variant (Ca(V)1.3(42A)). RT-PCR showed that expression of Ca(V)1.3(42A) mRNA is similar in both Wistar and WKY/SHR, but that the long variant (Ca(V)1.3(42)) is virtually absent in WKY/SHR. Thus I(Ca(e)) corresponds to the recruitment of Ca(V)1.3(42A) channels, unmasked by the absence of Ca(V)1.3(42) channels. Studies in WKY CCs do not report major functional alterations, despite the unusual expression pattern of Ca(V)1.3 splice variants. It remains to be established if more subtle functional alterations exist, and if the atypical splicing pattern of Ca(V)1.3 could be related to the functional and behavioral alterations reported in WKY/SHR rats, including their susceptibility to develop hypertension.     

A type of voltage-dependent Ca2+ channel on Vicia faba guard cell plasma membrane outwardly permeates K+

The fine regulation of stomatal aperture is important for both plant photosynthesis and transpiration, while stomatal closing is an essential plant response to biotic and abiotic stresses such as drought, salinity, wounding, and pathogens. Quick stomatal closing is primarily due to rapid solute loss. Cytosolic free calcium ([Ca(2+)](cyt)) is a ubiquitous second messenger, and its elevation or oscillation plays important roles in stomatal movements, which can be triggered by the opening of Ca(2+)-permeable channels on the plasma membrane. For Ca(2+)-permeable channel recordings, Ba(2+) is preferred as a charge-carrying ion because it has higher permeability to Ca(2+) channels and blocks K(+) channel activities to facilitate current recordings; however, it prevents visualization of Ca(2+) channels' K(+) permeability. Here, we employed Ca(2+) instead of Ba(2+) in recording Ca(2+)-permeable channels on Vicia faba guard cell plasma membrane to mimic physiological solute conditions inside guard cells more accurately. Inward Ca(2+) currents could be recorded at the single-channel level, and these currents could be inhibited by micromolar Gd(3+), but their reversal potential is far away from the theoretical equilibrium potential for Ca(2+). Further experiments showed that the discrepancy of the reversal potential of the recorded Ca(2+) currents is influenced by cytosolic K(+). This suggests that voltage-dependent Ca(2+) channels also mediate K(+) efflux at depolarization voltages. In addition, a new kind of high-conductance channels with fivefold to normal Ca(2+) channel and 18-fold to normal outward K(+) conductance was found. Our data presented here suggest that plants have their own saving strategies in their rapid response to stress stimuli, and multiple kinds of hyperpolarization-activated Ca(2+)-permeable channels coexist on plasma membranes.     

A model-independent algorithm to derive Ca2+ fluxes underlying local cytosolic Ca2+ transients

Local intracellular Ca(2+) signals result from Ca(2+) flux into the cytosol through individual channels or clusters of channels. To gain a mechanistic understanding of these events we need to know the magnitude and spatial distribution of the underlying Ca(2+) flux. However, this is difficult to infer from fluorescence Ca(2+) images because the distribution of Ca(2+)-bound dye is affected by poorly characterized processes including diffusion of Ca(2+) ions, their binding to mobile and immobile buffers, and sequestration by Ca(2+) pumps. Several methods have previously been proposed to derive Ca(2+) flux from fluorescence images, but all require explicit knowledge or assumptions regarding these processes. We now present a novel algorithm that requires few assumptions and is largely model-independent. By testing the algorithm with both numerically generated image data and experimental images of sparklets resulting from Ca(2+) flux through individual voltage-gated channels, we show that it satisfactorily reconstructs the magnitude and time course of the underlying Ca(2+) currents.     

Properties of a native cation channel activated by Ca2+ store depletion in vascular smooth muscle cells

Depletion of intracellular Ca(2+) stores activates capacitative Ca(2+) influx in smooth muscle cells, but the native store-operated channels that mediate such influx remain unidentified. Recently we demonstrated that calcium influx factor produced by yeast and human platelets with depleted Ca(2+) stores activates small conductance cation channels in excised membrane patches from vascular smooth muscle cells (SMC). Here we characterize these channels in intact cells and present evidence that they belong to the class of store-operated channels, which are activated upon passive depletion of Ca(2+) stores. Application of thapsigargin (TG), an inhibitor of sarco-endoplasmic reticulum Ca(2+) ATPase, to individual SMC activated single 3-pS cation channels in cell-attached membrane patches. Channels remained active when inside-out membrane patches were excised from the cells. Excision of membrane patches from resting SMC did not by itself activate the channels. Loading SMC with BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid), which slowly depletes Ca(2+) stores without a rise in intracellular Ca(2+), activated the same 3-pS channels in cell-attached membrane patches as well as whole cell nonselective cation currents in SMC. TG- and BAPTA-activated 3-pS channels were cation-selective but poorly discriminated among Ca(2+), Sr(2+), Ba(2+), Na(+), K(+), and Cs(+). Open channel probability did not change at negative membrane potentials but increased significantly at high positive potentials. Activation of 3-pS channels did not depend on intracellular Ca(2+) concentration. Neither TG nor a variety of second messengers (including Ca(2+), InsP3, InsP4, GTPgammaS, cyclic AMP, cyclic GMP, ATP, and ADP) activated 3-pS channels in inside-out membrane patches. Thus, 3-pS nonselective cation channels are present and activated by TG or BAPTA-induced depletion of intracellular Ca(2+) stores in intact SMC. These native store-operated cation channels can account for capacitative Ca(2+) influx in SMC and can play an important role in regulation of vascular tone.     

Concerted vs. sequential. Two activation patterns of vast arrays of intracellular Ca2+ channels in muscle

To signal cell responses, Ca(2+) is released from storage through intracellular Ca(2+) channels. Unlike most plasmalemmal channels, these are clustered in quasi-crystalline arrays, which should endow them with unique properties. Two distinct patterns of local activation of Ca(2+) release were revealed in images of Ca(2+) sparks in permeabilized cells of amphibian muscle. In the presence of sulfate, an anion that enters the SR and precipitates Ca(2+), sparks became wider than in the conventional, glutamate-based solution. Some of these were "protoplatykurtic" (had a flat top from early on), suggesting an extensive array of channels that activate simultaneously. Under these conditions the rate of production of signal mass was roughly constant during the rise time of the spark and could be as high as 5 microm(3) ms(-1), consistent with a release current >50 pA since the beginning of the event. This pattern, called "concerted activation," was observed also in rat muscle fibers. When sulfate was combined with a reduced cytosolic [Ca(2+)] (50 nM) these sparks coexisted (and interfered) with a sequential progression of channel opening, probably mediated by Ca(2+)-induced Ca(2+) release (CICR). Sequential propagation, observed only in frogs, may require parajunctional channels, of RyR isoform beta, which are absent in the rat. Concerted opening instead appears to be a property of RyR alpha in the amphibian and the homologous isoform 1 in the mammal.     

Characterization of plant phenotypes associated with loss-of-function of AtCNGC1, a plant cyclic nucleotide gated cation channel.

Of the 57 cation channel genes in the Arabidopsis genome, over a third encode cyclic nucleotide gated cation channels (CNGCs). CNGCs are ion channels regulated by cytosolic signaling molecules (cyclic nucleotides, calmodulin, and Ca(2+)), and which conduct Ca(2+) as well as K(+) and in some cases Na(+). Little is currently known about the role CNGCs may play in plant growth and development. Here, we examined the hypothesis that an Arabidopsis thaliana genotype containing a null mutation in one of the CGNC genes (AtCNGC1) would display cation uptake-related growth phenotype differences from wild type (WT) plants. We determined that AtCNGC1 protein is primarily expressed in the roots of Arabidopsis seedlings. Seedlings lacking this protein had slightly (6-22%) lower shoot Ca(2+) than WT plants. Primary roots of Atcngc1 mutant seedlings grew faster than roots of WT plants, and had larger angles of gravicurvature and less nitric oxide generation upon gravistimulation. We conclude that channels formed (at least in part) by AtCNGC1 contribute (along with other channels) to Ca(2+) uptake into plants, and that Ca(2+) uptake into roots through AtCNGC1 affects some aspects of growth in the primary root of Arabidopsis seedlings.     

Calumin, a Ca²⁺-binding protein on the endoplasmic reticulum, alters the ion permeability of Ca²⁺ release-activated Ca²⁺ (CRAC) channels

Store-operated channels (SOC) are Ca(2+)-permeable channels that are activated by IP(3)-receptor-mediated Ca(2+) depletion of the endoplasmic reticulum (ER). Recent studies identify a membrane pore subunits, Orai1 and a Ca(2+) sensor on ER, STIM1 as components of Ca(2+) release-activated Ca(2+) (CRAC) channels, which are well-characterized SOCs. On the other hand, proteins that act as modulators of SOC activity remain to be identified. Calumin is a Ca(2+)-binding protein that resides on the ER and functional experiments using calumin-null mice demonstrate that it is involved in SOC function, although its role is unknown. This study used electrophysiological analysis to explore whether calumin modulates CRAC channel activity. CRAC channel currents were absent in HEK293 cells co-expressing calumin with the CRAC channel components, Orai1 or STIM1. Meanwhile, HEK cells that co-expressed calumin with CRAC channels exhibited larger currents with slower inactivation than cells expressing CRAC channels alone. The current-voltage relationship showed an inwardly rectifying current, but a negative shift in the reversal potential of greater than 60mV was observed in HEK cells co-expressing calumin with CRAC channels. In addition, the permeability coefficient ratio of Ca(2+) over monovalent cations was much lower than that of cells expressing CRAC channels alone. Replacement of Na(+) with N-methyl-d-glucamine(+) in the external solution noticeably diminished the CRAC current in HEK cells co-expressing calumin and CRAC channels. In a Cs(+)-based external solution, CRAC current was not observed in either cell-type. In addition, Ca(2+) imaging analysis revealed that co-transfection of calumin reduced extracellular Ca(2+) influx via CRAC channels. Further, calumin was shown to be directly associated with CRAC channels. These results reveal a novel mechanism for the regulation of CRAC channels by calumin.     

Intracellular Ca2+ regulation in rat motoneurons during development

Changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) control the setting up of the neuro-muscular synapse in vitro and probably in vivo. Dissociated cultures of purified embryonic (E15) rat motoneurons were used to explore the molecular mechanisms by which endoplasmic reticulum Ca(2+) stores, via both ryanodine-sensitive and IP(3)-sensitive intracellular Ca(2+) channels control [Ca(2+)](i) homeostasis in these neurons during ontogenesis. Fura-2 microspectrofluorimetry monitorings in single neurons showed that caffeine-induced responses of [Ca(2+)](i) increased progressively from days 1-7 in culture. These responses were blocked by ryanodine and nicardipine but not by omega-conotoxin-GVIA or omega-conotoxin-MVIIC suggesting a close functional relationship between ryanodine-sensitive and L-type Ca(v)1 Ca(2+) channels. Moreover, after 6 days in vitro, neurons exhibited spontaneous or caffeine-induced Ca(2+) oscillations that were attenuated by nicardipine. In 1-day-old neurons, both thapsigargin or CPA, which deplete Ca(2+) stores from the endoplasmic reticulum, induced an increase in [Ca(2+)](i) in 75% of the neurons tested. The number of responding motoneurons declined to 25% at 5-6 days in vitro. Xestospongin-C, a membrane-permeable IP(3) receptor inhibitor blocked the CPA-induced [Ca(2+)](i) response in all stages. RT-PCR studies investigating the expression pattern of RYR and IP(3) Ca(2+) channels isoforms confirmed the presence of their different isoforms and provided evidence for a specific pattern of development for RYR channels during the first week in vitro. Taken together, present results show that the control of motoneuronal [Ca(2+)](i) homeostasis is developmentally regulated and suggest the presence of an intracellular ryanodine-sensitive Ca(2+) channel responsible for a Ca(2+)-induced Ca(2+) release in embryonic motoneurons following voltage-dependent Ca(2+) entry via L-type Ca(2+) channels.     

Ion channels and transporters in cancer. 4. Remodeling of Ca(2+) signaling in tumorigenesis: role of Ca(2+) transport

The Ca(2+) signal has major roles in cellular processes important in tumorigenesis, including migration, invasion, proliferation, and apoptotic sensitivity. New evidence has revealed that, aside from altered expression and effects on global cytosolic free Ca(2+) levels via direct transport of Ca(2+), some Ca(2+) pumps and channels are able to contribute to tumorigenesis via mechanisms that are independent of their ability to transport Ca(2+) or effect global Ca(2+) homeostasis in the cytoplasm. Here, we review some of the most recent studies that present evidence of altered Ca(2+) channel or pump expression in tumorigenesis and discuss the importance and complexity of localized Ca(2+) signaling in events critical for tumor formation.     

Ca(2+) signaling in dendritic spines

Dendritic spines are cellular microcompartments that are isolated from their parent dendrites and neighboring spines. Recently, imaging studies of spine Ca(2+) dynamics have revealed that Ca(2+) can enter spines through voltage-sensitive and ligand-activated channels, as well as through Ca(2+) release from intracellular stores. Relationships between spine Ca(2+) signals and induction of various forms of synaptic plasticity are beginning to be elucidated. Measurements of spine Ca(2+) concentration are also being used to probe the properties of single synapses and even individual calcium channels in their native environment.