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C Vergara

Publications and source records attributed to C Vergara.

At least 37 records · Page 2Linked to original sources

Current issues in invertebrate phototransduction. Second messengers and ion conductances.

Investigation of phototransduction in invertebrate photoreceptors has revealed many physiological and biochemical features of fundamental biological importance. Nonetheless, no complete picture of phototransduction has yet emerged. In most known cases, invertebrate phototransduction involves polyphosphoinositide and cyclic GMP (cGMP) intracellular biochemical signaling pathways leading to opening of plasma membrane ion channels. Excitation is Ca(2+)-dependent, as are adaptive feedback processes that regulate sensitivity to light. Transduction takes place in specialized subcellular regions, rich in microvilli and closely apposed to submicrovillar membrane systems. Thus, excitation is a highly localized process. This article focuses on the intracellular biochemical signaling pathways and the ion channels involved in invertebrate phototransduction. The coupling of signaling cascades with channel activation is not understood for any invertebrate species. Although photoreceptors have features that are common to most or all known invertebrate species, each species exhibits unique characteristics. Comparative electrophysiological, biochemical, morphological, and molecular biological approaches to studying phototransduction in these species lead to fundamental insights into cellular signaling. Several current controversies and proposed phototransduction models are evaluated.

Animals↗

Clinical and neuropathological study of six patients with spastic paraparesis associated with HTLV-I: an axomyelinic degeneration of the central nervous system.

Between 1990 to 1994, 6 TSP/HAM patients, 3 women and 3 men with an average age of 57.1 years (39 to 76 years old), who died in the Salvador Hospital were submitted to postmortem examination. The mean time of paraparesis was 7 years (3 to 17 years), and 2 patients had pseudobulbar signs. Three cases had macroscopic atrophy of the spinal cord. Histologically, all cases had lesions in the pyramidal tracts and 4 cases showed somatotopic lesions of the Goll's tracts which followed a "dying back" ascendant and descendant distribution, respectively. In 2 cases, both of which had intellectual impairment, demyelination of the subcortical and parathalamic areas was observed without U fiber involvement. Abnormal vessels with gross thickening of the adventitia, many of them with lymphocytic cuffs, were seen everywhere, especially in the spinal cord, brain stem, midbrain and meninges, but no relation between these findings and the parenchymal lesions was observed. Also, in the cases with posterior column involvement, neuronal changes and proliferation of satellite cells in the dorsal ganglia were found. All cases showed histological sialoadenitis and none had inflammatory muscle changes. We conclude that the lesions affected the neuraxis in a systemic axial fashion as in degenerative diseases, and did not seem to be secondary to vascular or inflammatory abnormalities.

Adult↗

Neural control of the expression of a Ca(2+)-activated K+ channel involved in the induction of myotonic-like characteristics.

1. Expression of the apamin-sensitive K+ channel (SK+) in rat skeletal muscle is neurally regulated. The regulatory effect of the nerve over the expression of some muscle ion channels has been attributed to the electrical activity triggered by the nerve and/or to a trophic effect of some molecules transported from the soma to the axonal endings. 2. SK+ channels apparently are involved in myotonic dystrophy (MD), therefore understanding the factors that regulate their expression may ultimately have important clinical relevance. 3. To establish if axoplasmic transport is involved in this process, we used two experimental approaches in adult rats: (a) Both sciatic nerves were severed, leaving a short or a long nerve stump attached to the anterior tibialis (AT). (b) Colchicine or vinblastine (VBL), two axonal transport blockers of different potencies, was applied on one leg to the sciatic nerve. To determine whether electrical activity affects the expression of SK+ channels, denervated AT were directly stimulated. The corresponding contralateral muscles were used as controls.

Animals↗

[Seroprevalence of HTLV-I in relatives of patients with spastic paraparesis (HAM/TSP and PEP)].

The seroprevalence of HTLV-1 was studied in parents, brothers, siblings and sexual partners of 147 patients with spastic paraparesis associated to HTLV-1 (HAM/TSP) and 84 patients with HTLV-1 negative spastic paraparesis (SP). Seroprevalence was 29.1% for HAM/SP and 0% for SP relatives (p < 0.001); the last figure is similar to that of the general population. Seroprevalence in sexual partners was 65%, suggesting that sexual intercourse is the principal route of transmission. Likewise, seroprevalence in siblings of mothers with HAM/TSP or HTLV-1 positive was 17.6%, suggesting a high maternal transmission.

Adolescent↗

Squamous cell carcinoma antigen (SCC Ag) in the diagnosis and prognosis of lung cancer.

OBJECTIVE: We have studied the usefulness of squamous cell carcinoma antigen (SCC Ag) in diagnosis and prognosis of lung cancer (LC). MATERIAL AND METHODS: We have measured the serum SCC Ag levels in 388 subjects: 69 healthy persons; 103 with nonmalignant lung diseases (NMLD); 24 with lung metastasis of extrapulmonary origin (LMEO); and 192 with LC (88, with squamous cell carcinoma [SCC] type). In 55 with SCC, we analyzed the survival time. RESULTS: Serum SCC Ag was above 2.5 ng/ml in 1.4 percent of healthy persons; 2.9 percent of those with NMLD; 8.3 percent of those with LMEO; and 27.6 percent of those with LC. Such percentage was 47.7 percent in SCC. In this type, there were significant differences according to the extent of disease (61.6 percent in advanced stages, and 26.5 percent in localized stages, p = 0.002). In the other types, the sensitivity was substantially lower. The initial SCC Ag has prognostic significance (p = 0.02) in the univariate analysis, but it loses such significance in a multivariate model, including the stage. CONCLUSIONS: Therefore, we do not recommend this marker in the clinical management of patients with LC, even it can be useful in the differential diagnosis if used in combination with other markers.

Adult↗

Microcin E492 forms ion channels in phospholipid bilayer membrane.

Microcin E492, a polypeptide antibiotic, has been shown to have an M(r) of 6,000 by urea-SDS-polyacrylamide gel electrophoresis of the fluorescently labelled compound. It is known that the bactericidal action of microcin involves a loss of the transmembrane potential. In this study we show that microcin forms cation-selective channels in planar phospholipid bilayers. The channels have two main conductance states the current-voltage curves of which rectify. The reversal potentials measured under biionic conditions indicate a permeability sequence of NH4+ > K+ = Rb+ = Cs+ > Na+ = Na+ = Li+ > Tris+. The results suggest that membrane potential dissipation induced by microcin is a consequence of the formation of pores in the bacterial membrane.

Anti-Bacterial Agents↗

Colchicine alters apamin receptors, electrical activity, and skeletal muscle relaxation.

A low conductance calcium-activated K+ channel is thought to regulate the rate of firing of several excitable cells. In skeletal muscle the expression of this channel is under nerve control. Previously, we reported that axonal flow blockade of rat nerves, induced by colchicine, caused a transient increase in muscle apamin receptors, determined by 125I-apamin binding to membrane fractions. The increase in apamin receptors was correlated with repetitive discharges resembling myotonic potentials in the electromyogram, that were blockable by apamin. Here we show that the increase in muscle apamin receptors and the alteration of the electromyogram are followed closely by a slowing of the twitch relaxation, that in turn, is decreased by apamin. Furthermore, the presence of myotonic-like alterations in the electromyogram and a slowing of muscle relaxation when muscle apamin receptors are increased suggests that these channels may participate, among other factors, in the generation of some kinds of myotonia.

Animals↗

Increase of apamin receptors in skeletal muscle induced by colchicine: possible role in myotonia.

We have shown an increase of apamin receptors in rat skeletal muscle membranes following the application of colchicine to the sciatic nerve. 125I-apamin binding to partially purified membrane fractions was observed since day 4, reached a maximum around days 6-15, and was negligible at day 35 after the application of colchicine. Control muscles (nerves treated with buffer solution) showed low binding values (11 fmol/mg protein). Maximal 125I-apamin binding values to partially purified muscle membranes of colchicine-treated rats (42 fmol/mg protein) were lower than those obtained in denervated muscle (95 fmol/mg protein). The affinity binding constant values were 37 (colchicine) and 95 pM (denervation). No signs of muscle denervation were observed on histological examination of the nerve submitted to colchicine treatment nor in the muscles innervated by it. Muscle tension developed by indirect stimulation was the same as in controls. We here show also that partially purified membranes of normal untreated muscles have measurable amounts of 125I-apamin binding (13 fmol/mg protein), similar to those obtained in control muscles. Electromyographic recordings of the muscles after colchicine treatment of the nerve showed abnormal repetitive electrical discharges, similar to myotonic discharges, that were present with a similar temporal course as the increase in apamin receptors. The myotonic-like discharges were suppressed by the topical application of apamin to the muscle, whereas the toxin had no effect on anthracene-9-carbolytic acid-induced myotonia. Our results suggest that a neurotrophic factor that travels by axonal flow is involved in the regulation of the expression of apamin receptors in skeletal muscle membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Light-dependent channels from excised patches of Limulus ventral photoreceptors are opened by cGMP.

The identity of the second messenger that directly activates the light-dependent conductance in invertebrate photoreceptors remains unclear; the available evidence provides some support for cGMP and Ca2+. To resolve this issue we have applied these second messengers to membrane patches excised from the light-sensitive lobe of Limulus ventral photoreceptors. Our results show that these patches contain channels that can be opened by cGMP, but not by Ca2+. These cGMP-activated channels closely resemble the channels activated by light in cell-attached patches. This evidence suggests that cGMP is the messenger that opens the light-dependent channel in invertebrate photoreceptors.

Animals↗

Multiple conductance states of the light-activated channel of Limulus ventral photoreceptors. Alteration of conductance state during light.

The properties of light-dependent channels in Limulus ventral photoreceptors have been studied in cell-attached patches. Two sizes of single-channel events are seen during illumination. Previous work has characterized the large (40 pS) events; the goal of the current work was to characterize the small (15 pS) events and determine their relationship to the large events. The small events are activated by light rather than as a secondary result of the change in membrane voltage during light. The mean open time of the small events is 1.34 +/- 0.49 ms (mean +/- SD, n = 15), approximately 50% of that of the large events. The large and small events have the same reversal potential and a similar dependence of open-state probability on voltage. Evidence that these events are due to different conductance states of the same channel comes from analysis of relatively infrequent events showing a direct transition between the 15 and 40-pS levels. Furthermore, large and small events do not superpose, even at positive voltages when the probability of being open is very high, as would be predicted if the two-sized events were due to independent channels. Expression of the different conductance states is not random; during steady illumination there are alternating periods of several hundred milliseconds in which there are consecutive, sequential large events followed by periods in which there are consecutive, sequential small events. At early times during the response to a step of light, the large conductance state is preferentially expressed. At later times, there is an increase in the relative contribution of the low conductance state. These findings indicate that there is a process that changes the preferred conductance state of the channel. This alteration has functional importance in the process of light adaptation.

Animals↗

Drug-induced fever: a clinical report and challenge test with calcium dobesilate.

A 54-year-old man was receiving calcium dobesilate for retinopathy and after 8 days he presented fever of more than 39 degrees C, generalized myalgia, chills and headache. Other causes of fever were ruled out. A challenge test was done with a single therapeutic oral dose of calcium dobesilate and fever appeared 20 h later and lasted 8 h. Our patient fulfils Young's stringent criteria for drug fever. To our knowledge drug-induced fever due to calcium dobesilate has not been reported previously.

Calcium Dobesilate↗

The nucleus basalis of Meynert in 20 definite cases of Creutzfeldt-Jakob disease.

The population of neurons and the neuronal size in the nucleus basalis of Meynert (nbM) were studied in 20 patients with definite Creutzfeldt-Jakob disease (CJD). When compared with a normal control group, the 20 CJD brains showed a significant loss of neurons and reduction of neuronal size, mainly in the middle level of the nbM and mostly affecting the right side. Since these findings show some parallelism with the amount of cortical damage and given the scarce gliosis and spongiosis found in only six of the 20 CJD brains, we postulate that the involvement of the nbM in CJD is a retrograde abnormality secondary to the damage of the neocortex.

Adult↗

Calcium-activated potassium channels of large unitary conductance.

The large unitary conductance Ca2+-activated K+ channel is a widely distributed channel in cellular membranes of diverse tissues. This type of channel may serve as a link between membrane excitability and cell metabolism. In this review we discuss some aspects of the gating mechanism, calcium activation and function and modulation of BK channels.

Animals↗

Effect of phospholipid surface charge on the conductance and gating of a Ca2+-activated K+ channel in planar lipid bilayers.

A Ca-activated, K-selective channel from plasma membrane of rat skeletal muscle was studied in artificial lipid bilayers formed from either phosphatidylethanolamine (PE) or phosphatidylserine (PS). In PE, the single-channel conductance exhibited a complex dependence on symmetrical K+ concentration that could not be described by simple Michaelis-Menten saturation. At low K+ concentrations the channel conductance was higher in PS membranes, but approached the same conductance observed in PE above 0.4 m KCl. At the same Ca2+ concentration and voltage, the probability of channel opening was significantly greater in PS than PE. The differences in the conduction and gating, observed in the two lipids, can be explained by the negative surface charge of PS compared to the neutral PE membrane. Model calculations of the expected concentrations of K+ and Ca2+ at various distances from a PS membrane surface, using Gouy-Chapman-Stern theory, suggest that the K+-conduction and Ca2+-activation sites sense a similar fraction of the surface potential, equivalent to the local electrostatic potential at a distance of 9 A from the surface.

Animals↗