Nonmodal gating of cardiac calcium channels as revealed by dihydropyridines

The hypothesis that dihydropyridine (DHP)-sensitive calcium channels have three distinct modes of gating has been examined. The major prediction is that the relative frequencies among modes depend on DHP concentration while the kinetics within a mode do not. We tested this by studying whole-cell and single-channel calcium currents in neonatal rat and adult guinea pig cardiac myocytes in different concentrations of several DHPs. In the absence of DHPs calcium currents declined with time but the kinetics, which are the focus of this study, were unchanged. Open-time frequency distributions had insignificant numbers of prolonged openings and were well fit by single tau's. Agonist DHP stereoisomers produced concentration-dependent changes in whole-cell tail current tau's. The frequency distribution of single calcium channel current open times became biexponential and the tau's were concentration dependent. The average number of openings per trace of channels with customary open times increased with increases in DHP concentration. Latencies to first opening for the customary openings and for prolonged openings were shorter in the presence of DHPs. A second larger conductance is another important feature of DHP-bound single calcium channels. Thus DHPs not only caused prolonged openings; they produced numerous changes in the kinetics of customary openings and increased channel conductance. It follows that these effects of DHPs do not support the hypothesis of modal gating of calcium channels. The mode model is not the only model excluded by the results; models in which DHPs are allowed to act only or mainly on open states are excluded, as are models in which the effects are restricted to inactivated states. We suggest a different type of model in which cooperative binding of DHPs at two sites produces the essential changes in kinetics and conductance.     

Fishers' Knowledge Reveals Ecological Interactions Between Fish and Plants in High Diverse Tropical Rivers

Ecosystems - Frugivory and seed dispersal by fish is an important mutualistic interaction in complex and species-rich tropical rivers. The local ecological knowledge (LEK) held by fishers can...     

Neurochemical effects ofl-pyroglutamic acid

The effect ofl-pyroglutamic acid, a metabolite that accumulates in pyroglutamic aciduria, on different neurochemical parameters was investigated in adult male Wistar rats. Glutamate binding, adenylate cyclase activity and G protein coupling to adenylate cyclase were assayed in the presence of the acid.l-pyroglutamic acid decreased Na⁺-dependent and Na⁺-independent glutamate binding Basal and GMP-PNP stimulated adenylate cyclase activity were not affected by the acid. Furthermore, rats received unilateral intrastriatal injections of 10–300 nmol of bufferedl-pyroglutamic acid. Vehicle (0.25 M Tris-Cl, pH 7.35–7.4) was injected into the contralateral striatum. Neurotoxic damage was assessed seven days after the injection by histological examination and by weighing both cerebral hemispheres. No difference in histology or weight could be identified between hemispheres. These results suggest that, although capable of interfering with glutamate binding, pyroglutamate did not cause a major lesion in the present model of neurotoxicity.     

Bioavailability of heavy metals in sediments of two coastal lagoons in Rio de Janeiro,Brazil

The distribution and bioavailability of trace metals in two contrasting tropical coastal lagoons were studied. The concentration of trace metals in aquatic macrophytes was compared with those found in sediments under weakly and strongly bound forms. The results showed that total metal concentrations in sediments did not explain the concentration found in plants. The highest concentrations in macrophytes were observed in the lagoon which had a higher fraction of metals weakly bound to sediments, but presented the lower total metal content. Low redox potential was the major variable keeping metals in non-bioavailable forms, possibly as refractory sulfides and metal-organic complexes. Among the macrophytes, rooted species showed lower concentrations of metals as compared to algae.     

Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel.

The skeletal muscle dihydropyridine receptor/Ca2+ channel is composed of five protein components (alpha 1, alpha 2 delta, beta, and gamma). Only two such components, alpha 1 and alpha 2, have been identified in heart. The present study reports the cloning and expression of a novel beta gene that is expressed in heart, lung, and brain. Coexpression of this beta with a cardiac alpha 1 in Xenopus oocytes causes the following changes in Ca2+ channel activity: it increases peak currents, accelerates activation kinetics, and shifts the current-voltage relationship toward more hyperpolarized potentials. It also increases dihydropyridine binding to alpha 1 in COS cells. These results indicate that the cardiac L-type Ca2+ channel has a similar subunit structure as in skeletal muscle, and provides evidence for the modulatory role of the beta subunit.     

S-adenosylmethionine induces mitochondrial dysfunction,permeability transition pore opening and redox imbalance in subcellular preparations of rat liver

Journal of Bioenergetics and Biomembranes - S-adenosylmethionine (AdoMet) predominantly accumulates in tissues and biological fluids of patients affected by liver dysmethylating diseases,...     

Inheritance of lambda-cyhalothrin resistance in the predator lady beetle Eriopis connexa (Germar) (Coleoptera: Coccinellidae)

Lambda-cyhalothrin is a pyrethroid insecticide widely used to control pests in various crop ecosystems, in which the lady beetle occurs naturally. Therefore, lady beetle populations are exposed to lambda-cyhalothrin sprays that may foster tolerance to this insecticide. This study was conducted to confirm the occurrence of resistance in the lady beetle Eriopis connexa (Germar) (Coleoptera: Coccinellidae) to lambda-cyhalothrin and to characterize the inheritance of resistance after eight progressive selection with insecticide dosages based on the LD₅₀ determined for the F1 generation. Dose–mortality curves were determined for parental populations, F1 hybrids and backcross progenies. Parameters regarding the heritability of resistance to lambda-cyhalothrin in E. connexa allow estimating 10-fold increase in the initial LD₅₀ after 54.5 generations of successive selections. The resistance of E. connexa to lambda-cyhalothrin was characterized as autosomally inherited and incompletely dominant, and influenced by a major gene with possible influence of secondary genes. Additionally, the resistance in E. connexa varies from functionally dominant to functionally recessive depending on the dose used. These findings indicate that insecticide resistance in E. connexa can be selected in the field as determined for field-collected individuals, and subsequently enhanced under laboratory conditions. Its characterization presented here is an important step toward linking biological and chemical control within pest management regarding the lady beetle and lambda-cyhalothrin targeting different pest groups.