Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by Gβγ subunits and function as heteromultimers

Guanine nucleotide-binding proteins (G proteins) activate K+ conductances in cardiac atrial cells to slow heart rate and in neurons to decrease excitability. cDNAs encoding three isoforms of a G-protein-coupled, inwardly rectifying K+ channel (GIRK) have recently been cloned from cardiac (GIRK1/Kir 3.1) and brain cDNA libraries (GIRK2/Kir 3.2 and GIRK3/Kir 3.3). Here we report that GIRK2 but not GIRK3 can be activated by G protein subunits Gβ1 and G2 in Xenopus oocytes. Furthermore, when either GIRK3 or GIRK2 was coexpressed with GIRK1 and activated either by muscarinic receptors or by Gβ subunits, G-protein-mediated inward currents were increased by 5- to 40-fold. The single-channel conductance for GIRK1 plus GIRK2 coexpression was intermediate between those for GIRK1 alone and for GIRK2 alone, and voltage-jump kinetics for the coexpressed channels displayed new kinetic properties. On the other hand, coexpression of GIRK3 with GIRK2 suppressed the GIRK2 alone response. These studies suggest that formation of heteromultimers involving the several GIRKs is an important mechanism for generating diversity in expression level and function of neurotransmitter-coupled, inward rectifier K+ channels

Intrinsic Gating Properties of a Cloned G Protein-activated Inward Rectifier K^+ Channel

The voltage-, time-, and K^+-dependent properties of a G protein-activated inwardly rectifying K^+ channel (GIRK1/KGA/Kir3.1) cloned from rat atrium were studied in Xenopus oocytes under two-electrode voltage clamp. During maintained G protein activation and in the presence of high external K^+ (V_K = 0 mV), voltage jumps from V_K to negative membrane potentials activated inward GIRK1 K^+ currents with three distinct time-resolved current components. GIRK1 current activation consisted of an instantaneous component that was followed by two components with time constants T_f~50 ms and T_s~400 ms. These activation time constants were weakly voltage dependent, increasing approximately twofold with maximal hyperpolarization from V_K. Voltage-dependent GIRK1 availability, revealed by tail currents at -80 mV after long prepulses, was greatest at potentials negative to V_K and declined to a plateau of approximately half the maximal level at positive voltages. Voltage-dependent GIRK1 availability shifted with V_K and was half maximal at V_K -20 mV; the equivalent gating charge was ~1.6 e^-. The voltage-dependent gating parameters of GIRK1 did not significantly differ for G protein activation by three heterologously expressed signaling pathways: m2 muscarinic receptors, serotonin 1A receptors, or G protein β1y2 subunits. Voltage dependence was also unaffected by agonist concentration. These results indicate that the voltage-dependent gating properties of GIRK1 are not due to extrinsic factors such as agonist-receptor interactions and G protein-channel coupling, but instead are analogous to the intrinsic gating behaviors of other inwardly rectifying K^+ channels

Quantum theory of the Intrinsic Orbital Magnetoelectric Effect in itinerant electron systems at finite temperatures

Magnetization can be induced by an electric field in systems without inversion symmetry $\mathcal{P}$ and time-reversal symmetry $\mathcal{T}$. This phenomenon is called the magnetoelectric (ME) effect. The spin ME effect has been actively studied in multiferroics. The orbital ME effect also exists and has been mainly discussed in topological insulators at zero temperature. In this paper, we study the intrinsic orbital ME response in metals at finite temperature using the Kubo formula. The intrinsic response originates from the Fermi sea and does not depend on the dissipation. Especially in systems with $\mathcal{PT}$-symmetry, the extrinsic orbital ME effect becomes zero, and the intrinsic ME effect is dominant. We apply the response tensor obtained in this work to a $\mathcal{PT}$-symmetric model Hamiltonian with antiferromagnetic loop current order demonstrating that the intrinsic ME effect is enhanced around the Dirac points

IXGAMES – Implementing Internet exchange point, exclusively for games

An ever-growing number of games is available on the market and more and more features are incorporated each day. The increase in the player base and game enhancements demand that games work on a network with reliable speed and efficient time response. This article proposes a high speed network infra-structure exclusive for games,. This network, called IXGAMES originated from experiments with shared routing through Internet Exchange Point (IXP). IXGAMES opens new business opportunities for operators/ Providers and game companies that, not only will provide financial return, but will also allow them to offer better quality service to their customersWorkshop de Arquitecturas, Redes y Sistemas Operativos (WARSO)Red de Universidades con Carreras en Informática (RedUNCI

Development of Film Dosage Form Containing Allopurinol for Prevention and Treatment of Oral Mucositis

Film dosage forms (FDs) containing allopurinol (AP) were prepared using a casting method with water-soluble polysaccharides, such as sodium alginate (ALG), and the release profile of AP from FDs was investigated in limited dissolution medium. Some ALGs were able to form FDs incorporating AP, and the thickness was about 50 μm. All FDs were easy to handle, though the rheological properties varied with ALG species. AP was homogenously present throughout the FDs and was released with disintegration in 10 mL of physiological saline. These results confirmed that FDs are useful for preventing or treating localized problems in the oral cavity, such as mucositis. FDs are also useful for administering drugs to cancer patients receiving chemotherapy and/or radiotherapy

Project Wireless Sensor Network Architecture for Tunnel Monitoring

Abstract: This paper presents an architecture for wireless sensor networks (WSN) operating in the 2.4GHz RF band for implementation in environments of small tunnels. The study begins with an objective description of the RF architecture and with the implementation of a RSSI analysis in real scenarios. The designed modules are using directional and omnidirectional antennas for each test scenario. In initial experiment is included a test on the 433Mhz band. The developed WSN architecture provides a higher degree of reliability at environments with denser structures (tunnels) and enables the use of directional and omnidirectional antennas for better signal behavior considering the structure of environment to propagation

Kir4.1 Potassium Channel Subunit Is Crucial for Oligodendrocyte Development and In Vivo Myelination

To understand the cellular and in vivo functions of specific K^+ channels in glia, we have studied mice with a null mutation in the weakly inwardly rectifying K^+ channel subunit Kir4.1. Kir4.1−/− mice display marked motor impairment, and the cellular basis is hypomyelination in the spinal cord, accompanied by severe spongiform vacuolation, axonal swellings, and degeneration. Immunostaining in the spinal cord of wild-type mice up to postnatal day 18 reveals that Kir4.1 is expressed in myelin-synthesizing oligodendrocytes, but probably not in neurons or glial fibrillary acidic protein-positive (GFAP-positive) astrocytes. Cultured oligodendrocytes from developing spinal cord of Kir4.1−/− mice lack most of the wild-type K^+ conductance, have depolarized membrane potentials, and display immature morphology. By contrast, cultured neurons from spinal cord of Kir4.1−/− mice have normal physiological characteristics. We conclude that Kir4.1 forms the major K^+ conductance of oligodendrocytes and is therefore crucial for myelination. The Kir4.1 knock-out mouse is one of the few CNS dysmyelinating or demyelinating phenotypes that does not involve a gene directly involved in the structure, synthesis, degradation, or immune response to myelin. Therefore, this mouse shows how an ion channel mutation could contribute to the polygenic demyelinating diseases

Eight types of stem cells in the life cycle of the moss Physcomitrella patens

Stem cells self-renew and produce cells that differentiate to become the source of the plant body. The moss Physcomitrella patens forms eight types of stem cells during its life cycle and serves as a useful model in which to explore the evolution of such cells. The common ancestor of land plants is inferred to have been haplontic and to have formed stem cells only in the gametophyte generation. A single stem cell would have been maintained in the ancestral gametophyte meristem, as occurs in extant basal land plants. During land plant evolution, stem cells diverged in the gametophyte generation to form different types of body parts, including the protonema and rhizoid filaments, leafy-shoot and thalloid gametophores, and gametangia formed in moss. A simplex meristem with a single stem cell was acquired in the sporophyte generation early in land plant evolution. Subsequently, sporophyte stem cells became multiple in the meristem and were elaborated further in seed plant lineages, although the evolutionary origin of niche cells, which maintain stem cells is unknown. Comparisons of gene regulatory networks are expected to give insights into the general mechanisms of stem cell formation and maintenance in land plants and provide information about their evolution. P. patens develops at least seven types of simplex meristem in the gametophyte and at least one type in the sporophyte generation and is a good material for regulatory network comparisons. In this review, we summarize recently revealed molecular mechanisms of stem cell initiation and maintenance in the moss. © 2013 Elsevier Ltd