Myosin calcium sensitivity

The major relaxing transmitters are those that elevate the cAMP or cGMP concentration (Fig. 3). Adenosine stimulates the activity of cAMP kinase. The next step is not clear, but evidence has been accumulated that cAMP kinase decreases the calcium sensitivity of the contractile machinery. In vitro, cAMP kinase phosphorylated MLCK and decreased thereby the affinity of MLCK for calcium-calmodulin. However, this regulation does not occur in intact smooth muscle. Possible other substrate candidates for cAMP kinase are the heat stable protein HSP 20, (A heat stable protein of 20 kDa that is phosphorylated by cGMP kinase. It has been postulated that phospho-HSP 20 interferes with the interaction between actin and myosin allowing thereby smooth muscle relaxation without dephosphorylation of the rMLC.) Rho A and MLCP that are phosphorylated also by cGMP kinase I (Fig. 3). 

The major regulatory proteins located on an actin filament are troponin and tropomyosin, each occupying 5% of the total myofibrillar proteins. Both proteins confer calcium sensitivity on the ATP-actin-myosin interactions (see Section II). There are minor regulatory proteins that modify the fine structures of myosin and actin filaments and also of Z lines. 

Hirano K, Phan BC, Hartshorne DJ (1997) Interactions of the subunits of smooth muscle myosin phosphatase. J Biol Chem 272 3683-3688 Hori M, Sato K, Miyamoto S, Ozaki H, Karaki H (1993) Different pathways of calcium sensitization activated by receptor agonists and phorbol esters in vascular smooth muscle. BrJ Pharmacol 110 1527-1531... 

The ETa receptor activates G proteins of the Gq/n and G12/i3 family. The ETB receptor stimulates G proteins of the G and Gq/11 family. In endothelial cells, activation of the ETB receptor stimulates the release of NO and prostacyclin (PGI2) via pertussis toxin-sensitive G proteins. In smooth muscle cells, the activation of ETA receptors leads to an increase of intracellular calcium via pertussis toxin-insensitive G proteins of the Gq/11 family and to an activation of Rho proteins most likely via G proteins of the Gi2/i3 family. Increase of intracellular calcium results in a calmodulin-dependent activation of the myosin light chain kinase (MLCK, Fig. 2). MLCK phosphorylates the 20 kDa myosin light chain (MLC-20), which then stimulates actin-myosin interaction of vascular smooth muscle cells resulting in vasoconstriction. Since activated Rho... 

Study of the molecular biology of calcium regulation of muscle contraction was initiated by the discovery of a new protein factor sensitizing actomyosin to calcium ions (Ebashi, 1963 Ebashi and Ebashi, 1964). This protein factor was called native tropomyosin, because of its similarity in amino acid composition to tropomyosin, which had been discovered earlier (Bailey, 1946, 1948). It was soon found that this factor is a complex of tropomyosin and a new globular protein, termed troponin (Ebashi and Kodama, 1965 Ebashi et al., 1968). Thus four proteins, i.e., myosin, actin, troponin, and tropomyosin, are involved in calcium-regulated physiological muscle contraction (Ebashi et al., 1968, 1969 Ebashi and Endo, 1968). The contractile interaction between myosin and actin is depressed by troponin and tropomyosin in the absence of calcium ions. When calcium ion acts on troponin, this depression is removed and the contractile interaction is then activated (Figs. 1 and 2). 

Troponin—A protein found predominately in cardiac, but not skeletal, muscle which regulates calcium-mediated interaction of actin and myosin. Troponin I and T are released into the blood from the myocytes at the time of myocardial cell necrosis secondary to infarction. These biochemical markers become elevated and are used in the diagnosis of myocardial infarction. Troponin I and T are more sensitive and specific for infarction that creatinine kinase which is found in both skeletal and myocardial cells. The exact value of troponin I or T which is diagnostic of infarction differs based upon assay. 

Pozzan T, Rizzuto R, Volpe P, Meldolesi J (1994) Molecular and cellular physiology of intracellular calcium stores. Physiol Rev 74 595-636 Raeymakers L, Wuytack F (1996) Calcium pumps. In Barany M (ed) Biochemistry of smooth muscle contraction. Academic Press, San Diego, pp 241-253 Rembold CM (1990) Modulation of the [Ca " ] sensitivity of myosin phosphorylation in intact swine arterial smooth muscle. J Physiol 429 77-94 Rembold CM, Weaver BA (1990) [Ca ], not diacylglycerol, is the primary regulator of sustained swine arterial smooth muscle contraction. Hypertension 15 692-698 Shimada T, Somlyo AP (1992) Modulation of voltage-dependent Ca channel current by arachidonic acid and other long-chain fatty acids in rabbit intestinal smooth muscle. J Gen Physiol 100 27-44... 

Blockade of potassium transport results in increased intracellular potassium Actin-myosin filaments are sensitized to calcium... 

---