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Myosin phosphatase isoforms as determinants of smooth muscle contractile function and calcium sensitivity of force

Rachael P Dippold1, Steven A Fisher

  • 1Department of Medicine (Cardiology), University of Maryland Baltimore, Baltimore, Maryland, USA.

Microcirculation (New York, N.Y. : 1994)
|October 12, 2013
PubMed

Insights

Myosin phosphatase (MP) subunit expression regulates smooth muscle tone. Specific splicing and transcription of MP subunits tune vascular responses to constrictors and dilators, impacting blood flow and pressure.

Area of Science:

  • Vascular Biology
  • Smooth Muscle Physiology
  • Molecular Pharmacology

Background:

  • Myosin phosphatase (MP) dephosphorylates myosin, inducing smooth muscle relaxation.
  • MP is a critical regulator of vascular tone, influencing blood flow and pressure.
  • The expression and function of MP subunits are key to vascular smooth muscle responses.

Purpose of the Study:

  • To review evidence supporting the hypothesis that regulated MP subunit expression determines smooth muscle responses.
  • To highlight the roles of Mypt1 Exon 24 splicing and CPI-17 transcription in vascular regulation.
  • To discuss the context-specific expression of MP subunits in the microcirculation and disease.

Main Methods:

  • Literature review of studies from the past two decades.
  • Analysis of existing data on MP subunit expression and vascular function.
  • Discussion of proposed mechanisms for MP subunit regulation of vascular tone.

Main Results:

  • Regulated expression of MP subunits is proposed as a critical determinant of smooth muscle responses.
  • Mypt1 Exon 24 splicing is suggested to modulate sensitivity to NO/cGMP-mediated relaxation.
  • CPI-17 transcription is proposed to dictate sensitivity to agonist-mediated constriction.

Conclusions:

  • MP subunit expression is context-specific in the microcirculation and varies with development and disease.
  • Current evidence is correlative; further studies are needed to confirm the hypothesis.
  • Generation of genetically engineered mice is proposed to validate the role of MP subunits in vascular function.
Keywords:
CPI-17Mypt1NOPKG1cGMPmyosin phosphatasevascular smooth muscle

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