Current Topics in the Regulatory Mechanism Underlying the Ca²⁺ Sensitization of the Contractile Apparatus in Vascular Smooth Muscle

Abstract

The Ca²⁺ signal is the primary determinant of the contraction of the vascular smooth muscle. However, the alteration of the Ca²⁺ sensitivity of the contractile apparatus also plays an essential role. The regulation of the myosin light chain phosphatase (MLCP) activity is considered to be the most important mechanism underlying the regulation of Ca²⁺ sensitivity. The investigations during the last 15 years have identified many proteins that participate in the regulation of the MLCP activity. Recently, the Ca²⁺ signal has also been shown to cross-talk with the mechanisms regulating the Ca²⁺ sensitivity. Consequently, Rho kinase, protein kinase C, CPI-17, and MYPT1 have all been suggested to play a physiologically important role in the regulation of the MLCP activity. We are now close to elucidating the major rules regulating the MLCP activity and the Ca²⁺ sensitivity during vascular contractions. This article will give an overview of the current understanding of the biochemical basis for the regulation of the MLCP activity, while also discussing their functional roles from a physiological point of view. I hope this article will help to develop new pharmacological strategies for the prevention and treatment of the pathological vasoconstriction often seen in vascular diseases.