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(Circulation Research. 2002;91:83.)
© 2002 American Heart Association, Inc.

Editorials

New Roads Leading to Ca²⁺ Sensitization

Avril V. Somlyo

From the Department of Molecular Physiology and Biological Physics, Department of Pathology, University of Virginia, Charlottesville, Va.

Correspondence to Avril V. Somlyo, Department of Molecular Physiology and Biological Physics, University of Virginia, PO Box 800736, Jordan Hall, Charlottesville, VA 22908-0736. E-mail avs5u@virginia.edu

Key Words: Rho-kinase • smooth muscle • vasospasm • sphingolipids • myosin phosphatase

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Gprotein–coupled receptors (GPCRs) activated by a wide variety of agonists can switch on myosin light chain phosphorylation and force in smooth muscle. The extent of myosin light chain phosphorylation reflects activity of both the Ca²⁺/calmodulin–dependent myosin light chain kinase (MLCK) and the myosin light chain phosphatase. Thus, at constant Ca²⁺ and MLCK activity, processes that inhibit myosin phosphatase activity cause a leftward shift of the Ca²⁺ force-response curve, a physiological relevant phenomenon known as Ca²⁺ sensitization.^1,2 There are two well-described myosin phosphatase inhibitory pathways. The first is through the small GTPase RhoA, in which GTP-bound RhoA translocates to the membrane and activates Rho-kinase that either directly or indirectly acts on the regulatory phosphatase subunit (MYPT-1) to inhibit phosphatase activity. The second signaling pathway, which is present in only some smooth muscles, is through phosphorylation of a phosphatase inhibitor, CPI-17 that, when phosphorylated, potently inhibits the catalytic subunit of myosin phosphatase.³ Crosstalk between the two pathways has been implicated from experiments using the Rho-kinase inhibitor Y-27632.⁴ A new signaling messenger of Ca²⁺ sensitization, which converges on the RhoA pathway at the level of Rho-kinase, is presented by Kobayashi and colleagues⁵ in this issue of Circulation Research: they demonstrate that sphingosylphosphorylcholine (SPC), a product of sphingomyelin deacylation, leads to an increase in force in the absence of an increase in the fura 2 Ca²⁺ signal. This force is inhibited by a Rho-kinase inhibitor, but not by inhibition of conventional or novel PKCs. Interestingly, the Ca²⁺-independent contraction was maintained for . . . [Full Text of this Article]

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