The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated T-cell pathway via interaction with the calcineurin A catalytic subunit

The calcineurin/nuclear factor of activated T-cell (NFAT) pathway represents a crucial transducer of cellular function. There is increasing evidence placing the sarcolemmal calcium pump, or plasma membrane calcium/calmodulin ATPase pump (PMCA), as a potential modulator of signal transduction pathways. We demonstrate a novel interaction between PMCA and the calcium/calmodulin-dependent phosphatase, calcineurin, in mammalian cells. The interaction domains were located to the catalytic domain of PMCA4b and the catalytic domain of the calcineurin A subunit. Endogenous calcineurin activity, assessed by measuring the transcriptional activity of its best characterized substrate, NFAT, was significantly inhibited by 60% in the presence of ectopic PMCA4b. This inhibition was notably reversed by the co-expression of the PMCA4b interaction domain, demonstrating the functional significance of this interaction. PMCA4b was, however, unable to confer its inhibitory effect in the presence of a calcium/calmodulin-independent constitutively active mutant calcineurin A suggesting a calcium/calmodulin-dependent mechanism. The modulatory function of PMCA4b is further supported by the observation that endogenous calcineurin moves from the cytoplasm to the plasma membrane when PMCA4b is overexpressed. We suggest recruitment by PMCA4b of calcineurin to a low calcium environment as a possible explanation for these findings. In summary, our results offer strong evidence for a novel functional interaction between PMCA and calcineurin, suggesting a role for PMCA as a negative modulator of calcineurin-mediated signaling pathways in mammalian cells. This study reinforces the emerging role of PMCA as a molecular organizer and regulator of signaling transduction pathways.

TRP Channels and calcium signalling in dental pulp stem cells

Introduction: Ca2+ ion is an important intracellular messenger essential for the regulation of various cellular functions including proliferation, differentiation and apoptosis. Transient Receptor Potential (TRP) channels are calcium permeable cationic channels that play important role in regulation of free intracellular calcium ([Ca2+]i) in response to thermal, physical and chemical stimuli. Ca2+ signalling in human dental pulp stem cells (hDPSCs) and the ion channels regulating Ca2+ are largely not known. Objectives: Investigate changes in [Ca2+]i and determine the ion channels that regulate calcium signalling in hDPSCs. Methods: DPSCs were derived from immature third molars and cells less than passage 6 were used in all the experiments. Changes in [Ca2+]i were studied with Fura2 calcium imaging. RNA was extracted from DPSCs and a panel of TRP channel gene expression was determined by qPCR employing custom designed FAM TRP specific primers and probes (Roche, UK) and the Light Cycler 480 Probes Master (Roche). Results: hDPSCs express gene transcripts for all TRP families including TRPV1, V2, V4, TRPA1, TRPC3, TRPC5, TRPC6, TRPM3, TRPM7 and TRPP2. Stimulation of cells with appropriate TRP channel agonist induced increase in [Ca2+]i and similar responses were obtained when cell were mechanically stimulated by membrane stretch with application of hypotonic solution. Conclusion: TRP channels mediate calcium signalling in hDPSCs that merit further investigation.

Ultra-high-resolution Observations of MHD Waves in Photospheric Magnetic Structures

Here we review the recent progress made in the detection, examination, characterisation and interpretation of oscillations manifesting in small-scale magnetic elements in the solar photosphere. This region of the Sun's atmosphere is especially dynamic, and importantly, permeated with an abundance of magnetic field concentrations. Such magnetic features can span diameters of hundreds to many tens of thousands of km, and are thus commonly referred to as the `building blocks' of the magnetic solar atmosphere. However, it is the smallest magnetic elements that have risen to the forefront of solar physics research in recent years. Structures, which include magnetic bright points, are often at the diffraction limit of even the largest of solar telescopes. Importantly, it is the improvements in facilities, instrumentation, imaging techniques and processing algorithms during recent years that have allowed researchers to examine the motions, dynamics and evolution of such features on the smallest spatial and temporal scales to date. It is clear that while these structures may demonstrate significant magnetic field strengths, their small sizes make them prone to the buffeting supplied by the ubiquitous surrounding convective plasma motions. Here, it is believed that magnetohydrodynamic waves can be induced, which propagate along the field lines, carrying energy upwards to the outermost extremities of the solar corona. Such wave phenomena can exist in a variety of guises, including fast and slow magneto-acoustic modes, in addition to Alfven waves. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate how wave motion is generated in the solar photosphere, which oscillatory modes are most prevalent, and the role that these waves play in supplying energy to various layers of the solar atmosphere.

Ultra-High-Resolution Observations of MHD Waves in Photospheric Magnetic Structures

This chapter reviews the recent observations of waves and oscillations manifesting in fine-scale magnetic structures in the solar photosphere, which are often interpreted as the "building blocks' of the magnetic Sun. The authors found, through phase relationships between the various waveforms, that small-scale magnetic bright points (MBPs) in the photosphere demonstrated signatures of specific magnetoacoustic waves, in particular the sausage and kink modes. Modern magnetohydrodynamic (MHD) simulations of the lower solar atmosphere clearly show how torsional motions can easily be induced in magnetic elements in the photosphere through the processes of vortical motions and/or buffeting by neighboring granules. The authors detected significant power associated with high-frequency horizontal motions, and suggested that these cases may be especially important in the creation of a turbulent environment that efficiently promotes Alfvén wave dissipation.

A Schamel equation for ion acoustic waves in superthermal plasmas

An investigation of the propagation of ion acoustic waves in nonthermal plasmas in the presence of trapped electrons has been undertaken. This has been motivated by space and laboratory plasma observations of plasmas containing energetic particles, resulting in long-tailed distributions, in combination with trapped particles, whereby some of the plasma particles are confined to a finite region of phase space. An unmagnetized collisionless electron-ion plasma is considered, featuring a non-Maxwellian-trapped electron distribution, which is modelled by a kappa distribution function combined with a Schamel distribution. The effect of particle trapping has been considered, resulting in an expression for the electron density. Reductive perturbation theory has been used to construct a KdV-like Schamel equation, and examine its behaviour. The relevant configurational parameters in our study include the superthermality index κ and the characteristic trapping parameter β. A pulse-shaped family of solutions is proposed, also depending on the weak soliton speed increment u₀. The main modification due to an increase in particle trapping is an increase in the amplitude of solitary waves, yet leaving their spatial width practically unaffected. With enhanced superthermality, there is a decrease in both amplitude and width of solitary waves, for any given values of the trapping parameter and of the incremental soliton speed. Only positive polarity excitations were observed in our parametric investigation.