Myosin light chain kinase controls voltage-dependent calcium channels in vascular smooth muscle

2013 ◽  
Vol 466 (7) ◽  
pp. 1377-1389 ◽  
Author(s):  
A. Martinsen ◽  
O. Schakman ◽  
X. Yerna ◽  
C. Dessy ◽  
N. Morel
Keyword(s):  
Smooth Muscle ◽  
Calcium Channels ◽  
Vascular Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

Regulation of vascular smooth muscle tone

1994 ◽  
Vol 72 (8) ◽  
pp. 919-936 ◽  
Author(s):  
Michael P. Walsh
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Contractile Response ◽  
Muscle Tone ◽  
Myosin Phosphorylation ◽  
Smooth Muscle Tone ◽  
Vascular Smooth Muscle Tone

Vascular smooth muscle tone is regulated primarily by the sarcoplasmic free Ca2+ concentration, which determines the level of myosin phosphorylation. Stimulation of the muscle results in an increase in free [Ca2+], whereupon Ca2+ binds to calmodulin, inducing a conformational change enabling calmodulin to interact with and activate myosin light chain kinase. The active Ca2+∙calmodulin∙myosin light chain kinase complex catalyses the phosphorylation of serine-19 of the two 20-kDa light chains of myosin; this triggers cross-bridge cycling and the development of force. Relaxation follows restoration of free [Ca2+] to the resting level, whereupon calmodulin dissociates from myosin light chain kinase, which is thereby inactivated, and myosin is dephosphorylated by myosin light chain phosphatase and remains detached from actin. Overwhelming evidence now exists in favour of the central role of myosin phosphorylation–dephosphorylation in smooth muscle contraction–relaxation. However, considerable evidence supports the existence of additional, secondary mechanisms that can modulate the contractile state of smooth muscle either by altering the Ca2+ sensitivity of the contractile response or otherwise modulating one of the molecular events occurring downstream of the Ca2+ signal, e.g., the interaction of phosphorylated myosin heads with actin. The interplay of several regulatory elements confers on the contractile response of vascular smooth muscle the high degree of flexibility and adaptability required for the effective regulation of blood pressure.Key words: calcium, myosin, protein kinases, protein phosphatases, signal transduction, regulation of contraction, caldesmon, calponin.

Cyclic nucleotide dependent relaxation in vascular smooth muscle

1994 ◽  
Vol 72 (11) ◽  
pp. 1380-1385 ◽  
Author(s):  
Nancy L. McDaniel ◽  
Christopher M. Rembold ◽  
Richard A. Murphy
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Light Chain ◽  
Cyclic Nucleotide ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Regulatory Light Chain ◽  
Myosin Phosphorylation ◽  
Cross Bridge ◽  
The Relationship

Although not without controversy, the mechanisms inducing contraction of vascular smooth muscle are relatively well defined. There is a stimulus-induced increase in myoplasmic [Ca2+] with activation of myosin light chain kinase by the Ca2+–calmodulin complex, phosphorylation of the 20-kDa regulatory light chain of myosin, with subsequent cross-bridge cycling and force development. Ca2+-dependent phosphorylation of the myosin regulatory light chain appears to be the primary mechanism responsible for regulating stress in vascular smooth muscle. The relationship between myoplasmic [Ca2+] and myosin phosphorylation (i.e., the calcium sensitivity of phosphorylation) is regulated. It is higher with agonist stimulation than in tissues depolarized with high potassium solutions or after skinning procedures. The relationship between myosin phosphorylation and stress appears to be invariant with physiologic stimulation. This suggests that cross-bridge phosphorylation normally determines contraction. The mechanisms of relaxation are less well defined. In the most simple scheme, reduction of myoplasmic [Ca2+] with a fall in myosin light chain kinase activity would suffice to account for dephosphorylation of the regulatory light chain and relaxation. However, other mechanisms have been implicated in cyclic nucleotide dependent relaxation in vascular and other smooth muscle tissues. The current hypotheses of the mechanism of cyclic nucleotide dependent relaxation in vascular smooth muscle are reviewed.Key words: calcium, cyclic adenosine 3′,5′-monophosphate, cyclic guanosine 3′,5′-monophosphate, myosin light chain phosphorylation, vasodilation.

Sign in / Sign up

Export Citation Format

Share Document