The FDA first approved Invokana as the first SGLT2 drug in March 2013. Since then, it has become a cash cow for J&J and its Janssen Pharmaceuticals unit. In the first quarter of 2015, the drug already brought in $278 million, triple what it made last year.
During contraction, the smooth-muscle cell's intermediate filaments help to draw the cell up, like closing a drawstring purse. Calcium ions regulate contraction in smooth muscle, but they do it in a slightly different way than in skeletal muscle: 1  Calcium ions come from outside of the cell.2  Calcium ions bind to an enzyme complex on myosin, called calmodulin-myosin light chain kinase. Calcium ions come from outside of the cell. 2  Calcium ions bind to an enzyme complex on myosin, called calmodulin-myosin light chain kinase. 3  The enzyme complex breaks up ATP into ADP and transfers the P i directly to myosin. 4  This P i transfer activates myosin.
This calcium then binds to troponin, causing tropomyosin to move and allowing cross-bridges to form between the myosin and actin filaments. The actin is then pulled (slides) across the myosin. Unlike skeletal muscle, there is no neuromuscular junction or troponin in smooth muscle.Instead, contraction is started by the release of neurotransmitter vesicles (membrane bound containers) into the space between the cells. In smooth muscle calcium acts directly on the myosin head-causing cross-bridges to form. Thick filaments are scattered throughout the sarcoplasm of a smooth muscle cell. The myosin proteins are organized differently than in skeletal or cardiac muscle cells, and smooth muscle cells have more cross-bridges per thick filament.