Background: The multisubunit (α 1S ,α 2 -δ, β 1a and γ 1 ) skeletal muscle dihydropyridine receptor (DHPR) transduces membrane depolarization into release of Ca 2+ from the sarcoplasmic reticulum (SR) and also acts as an L-type Ca 2+ channel. To more fully investigate the function of the γ 1 subunit in these two processes, we produced mice lacking this subunit by gene targeting.
Background: The L-type Ca 2+ channel formed by the dihydropyridine receptor (DHPR) of skeletal muscle senses the membrane voltage and opens the ryanodine receptor (RyR1). This channel-to-channel coupling is essential for Ca 2+ signaling but poorly understood. We characterized a single-base frame-shift mutant of α 1S , the pore subunit of the DHPR, that has the unusual ability to function voltage sensor for excitation-contraction (EC) coupling by virtue of expressing two complementary hemi-Ca 2+ channel fragments.
Abstract. This study presents a landslide susceptibility map using an artificial intelligence (AI) approach based on standards set by the INSPIRE (Infrastructure for Spatial Information in the European Community) framework. INSPIRE is a European Union spatial data infrastructure (SDI) initiative to standardize spatial data across borders to ensure interoperability for management of cross-border infrastructure and environmental issues. However, despite the theoretical effectiveness of the SDI, few real-world applications make use of INSPIRE standards. In this study, we show how INSPIRE standards enhance the interoperability of geospatial data and enable deeper knowledge development for their interpretation and explainability in AI applications. We designed an ontology of landslides, embedded with INSPIRE vocabularies, and then aligned geology, stream network, and land cover datasets covering the Veneto region of Italy to the standards. INSPIRE was formally extended to include an extensive landslide type code list, a landslide size code list, and the concept of landslide susceptibility to describe map application inputs and outputs. Using the terms in the ontology, we defined conceptual scientific models of areas likely to generate different types of landslides as well as map polygons representing the land surface. Both landslide models and map polygons were encoded as semantic networks and, by qualitative probabilistic comparison between the two, a similarity score was assigned. The score was then used as a proxy for landslide susceptibility and displayed in a web map application. The use of INSPIRE-standardized vocabularies in ontologies that express scientific models promotes the adoption of the standards across the European Union and globally. Further, this application facilitates the explanation of the generated results. We conclude that public and private organizations, within and outside the European Union, can enhance the value of their data by making them INSPIRE-compliant for use in AI applications.
difference in current density between long and short channels for both Ba 2þ and Ca 2þ currents (I Ba and I Ca ) while membrane expression of the pore-forming subunit was unchanged suggesting additional differences of unitary current properties. To further determine the mechanism underlying CTM modulation, we performed single-channel analysis of recombinant long (Ca V 1.3 42 ) or short (Ca V 1.3 42A ) channels co-expressed with b 3 and a 2 d-1 in HEK-293 cells using either15mM Ba 2þ or Ca 2þ as charge carrier. We found a significant increase of channel availability given as fraction of active sweeps [%] (at À30mV for Ca V 1.3 42 : 20.953.1, Ca V 1.3 42A : 60.959.7, p<0.01, Students t-test) which reflects the shift to hyperpolarized potentials of Ca V 1.3 42A channels in whole-cell experiments. Furthermore, larger currents in Ca V 1.3 42A channels were due to significantly increased open probability across all test potentials. Single-channel conductance was similar (16 and 15 pS for Ca V 1.3 42 and Ca V 1.3 42A ). The inactivation of ensemble average I Ba was similarly slow in both channels. In contrast, more pronounced single-channel I Ca inactivation of Ca V 1.3 42A compared to Ca V 1.3 42 was found (t inact [ms] at À10mV: Ca V 1.3 42 : 35.5512.3, Ca V 1.3 42A : 8.253.1).Taken together, single-channel properties reflect the differences in voltage-and Ca 2þ -dependent activation and inactivation gating properties previously observed in whole-cell recordings for these two splice variants. We could explain the higher current density of Ca V 1.3 42A channels by increased channel activity.
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