Evidence for the interaction of Endophilin A3 with endogenous K(Ca)2.3 channels in PC12 cells

Background/Aims: Small-conductance calcium-activated (SK) channels play an important role by controlling the after-hyperpolarization of excitable cells. The level of expression and density of these channels is an essential factor for controlling different cellular functions. Several studies showed a co-localization of KCa2.3 channels and Endophilin A3 in different tissues. Endophilin A3 belongs to a family of BAR- and SH3 domain containing proteins that bind to dynamin and are involved in the process of vesicle scission in clathrin-mediated endocytosis. Methods: Using the yeast two-hybrid system and the GST pull down assay we demonstrated that Endophilin A3 interacts with the N-terminal part of KCa2.3 channels. In addition, we studied the impact of this interaction on channel activity by patch clamp measurements in PC12 cells expressing endogenous KCa2.3 channels. KCa2.3 currents were activated by using pipette solutions containing 1 µM free Ca(2+). Results: Whole-cell measurements of PC12 cells transfected with Endophilin A3 showed a reduction of KCa2.3 specifc Cs(+) currents indicating that the interaction of Endophilin A3 with KCa2.3 channels also occurs in mammalian cells and that this interaction has functional consequences for current flowing through KCa2.3 channels. Since KCa2.3 specific currents could be increased in PC12 cells transfected with Endophilin A3 with DC-EBIO (30 µM), a known SK-channel activator, these data also implicate that Endophilin A3 did not significantly remove KCa2.3 channels from the membrane but changed the sensitivity of the channels to Ca(2+) which could be overcome by DC-EBIO. Conclusion: This interaction seems to be important for the function of KCa2.3 channels and might therefore play a significant role in situations where channel activation is pivotal for cellular function

Localized f electrons in CexLa1-xRhIn5: dHvA Measurements

Measurements of the de Haas-van Alphen effect in CexLa1-xRhIn5 reveal that the Ce 4f electrons remain localized for all x, with the mass enhancement and progressive loss of one spin from the de Haas-van Alphen signal resulting from spin fluctuation effects. This behavior may be typical of antiferromagnetic heavy fermion compounds, inspite of the fact that the 4f electron localization in CeRhIn5 is driven, in part, by a spin-density wave instability.Comment: 4 pages, 4 figures, submitted to PR

Vortex Dynamics and Defects in Simulated Flux Flow

We present the results of molecular dynamic simulations of a two-dimensional vortex array driven by a uniform current through random pinning centers at zero temperature. We identify two types of flow of the driven array near the depinning threshold. For weak disorder the flux array contains few dislocation and moves via correlated displacements of patches of vortices in a {\it crinkle} motion. As the disorder strength increases, we observe a crossover to a spatially inhomogeneous regime of {\it plastic} flow, with a very defective vortex array and a channel-like structure of the flowing regions. The two regimes are characterized by qualitatively different spatial distribution of vortex velocities. In the crinkle regime the distribution of vortex velocities near threshold has a single maximum that shifts to larger velocities as the driving force is increased. In the plastic regime the distribution of vortex velocities near threshold has a clear bimodal structure that persists upon time-averaging the individual velocities. The bimodal structure of the velocity distribution reflects the coexistence of pinned and flowing regions and is proposed as a quantitative signature of plastic flow.Comment: 12 pages, 13 embedded PostScript figure

Cerebral malaria: in praise of epistemes

10.1016/j.pt.2010.03.005Trends in Parasitology266275-277TPRA

Sterile protection against malaria is independent of immune responses to the circumsporozoite protein

10.1371/journal.pone.0001371PLoS ONE212e137

Breadth of humoral response and antigenic targets of sporozoite-inhibitory antibodies associated with sterile protection induced by controlled human malaria infection.

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