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Dynamic L-type CaV1.2 channel trafficking facilitates CaV1.2 clustering and cooperative gating.
L-type CaV1.2 channels are key regulators of gene expression, cell excitability and muscle contraction. CaV1.2 channels organize in clusters throughout the plasma membrane. This channel organization has been suggested to contribute to the concerted activation of adjacent CaV1.2 channels (e.g. cooperative gating). Here, we tested the hypothesis that dynamic intracellular and perimembrane trafficking of CaV1.2 channels is critical for formation and dissolution of functional channel clusters mediating cooperative gating. We found that CaV1.2 moves in vesicular structures of circular and tubular shape with diverse intracellular and submembrane trafficking patterns. Both microtubules and actin filaments are required for dynamic movement of CaV1.2 vesicles. These vesicles undergo constitutive homotypic fusion and fission events that sustain CaV1.2 clustering, channel activity and cooperative gating. Our study suggests that CaV1.2 clusters and activity can be modulated by diverse and unique intracellular and perimembrane vesicular dynamics to fine-tune Ca2+ signals
Dynamic Changes in Sarcoplasmic Reticulum Structure in Ventricular Myocytes
The fidelity of excitation-contraction (EC) coupling in ventricular myocytes is remarkable, with each action potential evoking a [Ca2+]i transient. The prevalent model is that the consistency in EC coupling in ventricular myocytes is due to the formation of fixed, tight junctions between the
sarcoplasmic reticulum (SR) and the sarcolemma where Ca2+ release is activated. Here, we tested the hypothesis that the SR is a structurally inert organelle in ventricular myocytes. Our data suggest that rather than being static, the SR undergoes frequent dynamic structural changes. SR boutons expressing functional ryanodine receptors moved throughout the cell, approaching or moving away from the sarcolemma of ventricular myocytes. These changes in SR structure occurred in the absence of changes in [Ca2+]i during EC coupling. Microtubules and the molecular motors dynein and kinesin 1(Kif5b) were important regulators of SR motility. These findings support a model in which the SR is a motile organelle capable of molecular motor protein-driven structural changes
Autoimmune neurological conditions associated with Zika virus infection
Zika virus (ZIKV) is an emerging flavivirus rapidly spreading throughout the tropical Americas. mosquitoes is the principal way of transmission of the virus to humans. ZIKV can be spread by transplacental, perinatal, and body fluids. ZIKV infection is often asymptomatic and those with symptoms present minor illness after 3 to 12 days of incubation, characterized by a mild and self-limiting disease with low-grade fever, conjunctivitis, widespread pruritic maculopapular rash, arthralgia and myalgia. ZIKV has been linked to a number of central and peripheral nervous system injuries such as Guillain-Barré syndrome (GBS), transverse myelitis (TM), meningoencephalitis, ophthalmological manifestations, and other neurological complications. Nevertheless, mechanisms of host-pathogen neuro-immune interactions remain incompletely elucidated. This review provides a critical discussion about the possible mechanisms underlying the development of autoimmune neurological conditions associated with Zika virus infection
Phosphoinositide 3-Kinase Binds to TRPV1 and Mediates NGF-stimulated TRPV1 Trafficking to the Plasma Membrane
Sensitization of the pain-transducing ion channel TRPV1 underlies thermal hyperalgesia by proalgesic agents such as nerve growth factor (NGF). The currently accepted model is that the NGF-mediated increase in TRPV1 function during hyperalgesia utilizes activation of phospholipase C (PLC) to cleave PIP2, proposed to tonically inhibit TRPV1. In this study, we tested the PLC model and found two lines of evidence that directly challenge its validity: (1) polylysine, a cationic phosphoinositide sequestering agent, inhibited TRPV1 instead of potentiating it, and (2) direct application of PIP2 to inside-out excised patches dramatically potentiated TRPV1. Furthermore, we show four types of experiments indicating that PI3K is physically and functionally coupled to TRPV1: (1) the p85β subunit of PI3K interacted with the N-terminal region of TRPV1 in yeast 2-hybrid experiments, (2) PI3K-p85β coimmunoprecipitated with TRPV1 from both HEK293 cells and dorsal root ganglia (DRG) neurons, (3) TRPV1 interacted with recombinant PI3K-p85 in vitro, and (4) wortmannin, a specific inhibitor of PI3K, completely abolished NGF-mediated sensitization in acutely dissociated DRG neurons. Finally, simultaneous electrophysiological and total internal reflection fluorescence (TIRF) microscopy recordings demonstrate that NGF increased the number of channels in the plasma membrane. We propose a new model for NGF-mediated hyperalgesia in which physical coupling of TRPV1 and PI3K in a signal transduction complex facilitates trafficking of TRPV1 to the plasma membrane
Wavelength calibration of Brewer spectrophotometer using a tunable pulsed laser and implications to the Brewer ozone retrieval
In this contribution we present the wavelength calibration of the travelling reference Brewer spectrometer of the Regional Brewer Calibration Center for Europe (RBCCE) at PTB in Braunschweig, Germany. The wavelength calibration is needed for the calculation of the ozone absorption coefficients used by the Brewer ozone algorithm. In order to validate the standard procedure for determining Brewer’s wavelength scale, a calibration has been performed by using a tunable laser source at PTB in the framework of the EMRP project ENV59 ATMOZ “Traceability for the total column ozone”. Here we compare these results to those of the standard procedure for the wavelength calibration of the Brewer instrument. Such a comparison allows validating the standard methodology used for measuring the ozone absorption coefficient with respect to several assumptions. The results of the laser-based calibrations reproduces those obtained by the standard operational methodology and shows that there is an underestimation of 0.8 % of the ozone absorption coefficients due to the use of the parametrized slit functions.This work has been supported by the European Metrology Research Programme (EMRP) within the joint research project ENV59 “Traceability for atmospheric total column ozone” (ATMOZ). The EMRP is jointly funded by the EMRP participating countries within EURAMET and the European Union
Stability of the RBCC-E Triad during the period 2005 - 2015
Póster elaborado para el Quadrennial Ozone Symposium celebrado en Edinburgh los días 4–9 de septiembre de 2016
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