Furthermore, we found that the nonconserved, distal C terminus of β 1a plays a pivotal role in reconstitution of DHPR tetrads and thus allosteric DHPR–RyR1 interaction, essential for skeletal muscle EC coupling.Įxcitation–contraction (EC) coupling in skeletal muscle is initiated by depolarization of the muscle cell membrane induced by motor neuron input, which subsequently induces myofibril contractions. Conversely, gain-of-function chimera β 4/β 1a(C) with β 1a C terminus completely restored cytoplasmic Ca 2+ transients, DHPR tetrads, and motility. However, chimera β 1a/β 4(C) with β 4 C terminus produced significantly reduced cytoplasmic Ca 2+ transients. β 1a/β 4 chimeras with either N terminus, SH3, HOOK, or GK domain derived from β 4 showed complete restoration of SR Ca 2+ release. To investigate the molecular region(s) of β 1a responsible for the tetradic arrangement of DHPRs and thus DHPR–RyR1 coupling, we expressed loss- and gain-of-function chimeras between β 1a and β 4, with systematically swapped domains in zebrafish strain relaxed (β 1-null) for patch clamp, cytoplasmic Ca 2+ transients, motility, and freeze-fracture electron microscopy. Thus, all β-subunits are able to restore triad targeting, but only β 1a restores both tetrads and proper DHPR–RyR1 coupling. Consequently, β 3 failed to restore EC coupling despite the fact that both β 3 and β 1a restore tetrads. Previously, we showed that all four vertebrate β isoforms (β 1–β 4) facilitate α 1S triad targeting and, except for β 3, fully enable DHPRα 1S voltage sensing. These three features are obligatory for skeletal muscle excitation–contraction (EC) coupling. Twenty-first Century, in Atlanta, history is being written.The skeletal muscle dihydropyridine receptor (DHPR) β 1a subunit is indispensable for full trafficking of DHPRs into triadic junctions (i.e., the close apposition of transverse tubules and sarcoplasmic reticulum ), facilitation of DHPRα 1S voltage sensing, and arrangement of DHPRs into tetrads as a consequence of their interaction with ryanodine receptor (RyR1) homotetramers. Pei, and Marcel Breuer have reshaped the city's profile. Since the late 1970s, dozens of dazzling skyscrapers designed by such luminaries as Philip Johnson, I. A good measure of this growth is the ever-changing downtown skyline, along with skyscrapers constructed in the Midtown, Buckhead, and outer perimeter (fringing I-285) business districts. In the past two decades, Atlanta has experienced unprecedented growth - the official city population remains steady, at about 420,000, but the metro population has grown in the past decade by nearly 40 percent, from 2.9 million to 4.1 million people. Atlanta has become the best example of the New South, a fast-paced modern city proud of its heritage. And because of them, Atlanta became a fast-paced modern city which opened its doors to the 1996 Olympics.ĭie-hard southerners view Atlanta as the heart of the Old Confederacy. They made monumental sacrifices for that peace. Civil rights leaders moved forward they were the visionaries who saw a new South, a new Atlanta. In the turbulent 60s, Atlanta was "the city too busy to hate." And today, in the 21st century, Atlanta is the "city not too busy to care.”įor more than four decades, Atlanta has been linked to the civil rights movement. The old in new Atlanta is the soul of the city, the heritage that enhances the quality of life in a contemporary city. Atlanta is the capital city of the Southeast, a city of the future with strong ties to its past. The city has emerged as a banking center and boasts the third largest concentration of Fortune 500 companies in the country. Direct flights to Europe, South America, and Asia have made metro Atlanta easily accessible to the more than 1,000 international businesses that operate here and the more than 50 countries that have representation in the city through consulates, trade offices, and chambers of commerce. Today the fast-growing city remains a transportation hub, not just for the country but also for the world: Hartsfield-Jackson Atlanta International Airport is the world's busiest in daily passenger flights. Atlanta has a long, rich history, some of which is touched upon on this page.Ītlanta was founded in 1837 as the end of the Western & Atlantic railroad line (it was first named Marthasville in honor of the then-governor's daughter, nicknamed Terminus for its rail location, and then changed soon after to Atlanta, the feminine of Atlantic - as in the railroad).
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