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Calcium-independent phospholipase A2 participates in KCl-induced calcium sensitization of vascular smooth muscle.

Publication ,  Journal Article
Ratz, PH; Miner, AS; Barbour, SE
Published in: Cell Calcium
July 2009

In vascular smooth muscle, KCl not only elevates intracellular free Ca(2+) ([Ca(2+)](i)), myosin light chain kinase activity and tension (T), but also can inhibit myosin light chain phosphatase activity by activation of rhoA kinase (ROCK), resulting in Ca(2+) sensitization (increased T/[Ca(2+)](i) ratio). Precisely how KCl causes ROCK-dependent Ca(2+) sensitization remains to be determined. Using Fura-2-loaded isometric rings of rabbit artery, we found that the Ca(2+)-independent phospholipase A(2) (iPLA(2)) inhibitor, bromoenol lactone (BEL), reduced the KCl-induced tonic but not early phasic phase of T and potentiated [Ca(2+)](i), reducing Ca(2+) sensitization. The PKC inhibitor, GF-109203X (> or =3 microM) and the pseudo-substrate inhibitor of PKCzeta produced a response similar to BEL. BEL reduced basal and KCl-stimulated myosin phosphatase phosphorylation. Whereas BEL and H-1152 produced strong inhibition of KCl-induced tonic T (approximately 50%), H-1152 did not induce additional inhibition of tissues already inhibited by BEL, suggesting that iPLA(2) links KCl stimulation with ROCK activation. The cPLA(2) inhibitor, pyrrolidine-1, inhibited KCl-induced tonic increases in [Ca(2+)](i) but not T, whereas the inhibitor of 20-HETE production, HET0016, acted like the ROCK inhibitor H-1152 by causing Ca(2+) desensitization. These data support a model in which iPLA(2) activity regulates Ca(2+) sensitivity.

Duke Scholars

Published In

Cell Calcium

DOI

EISSN

1532-1991

Publication Date

July 2009

Volume

46

Issue

1

Start / End Page

65 / 72

Location

Netherlands

Related Subject Headings

  • rho-Associated Kinases
  • Rabbits
  • Pyrrolidines
  • Pyrones
  • Protein Kinase C
  • Potassium Chloride
  • Phospholipases A2, Calcium-Independent
  • Phenylephrine
  • Naphthalenes
  • Myosin-Light-Chain Kinase
 

Citation

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Ratz, P. H., Miner, A. S., & Barbour, S. E. (2009). Calcium-independent phospholipase A2 participates in KCl-induced calcium sensitization of vascular smooth muscle. Cell Calcium, 46(1), 65–72. https://doi.org/10.1016/j.ceca.2009.05.001
Ratz, Paul H., Amy S. Miner, and Suzanne E. Barbour. “Calcium-independent phospholipase A2 participates in KCl-induced calcium sensitization of vascular smooth muscle.Cell Calcium 46, no. 1 (July 2009): 65–72. https://doi.org/10.1016/j.ceca.2009.05.001.
Ratz, Paul H., et al. “Calcium-independent phospholipase A2 participates in KCl-induced calcium sensitization of vascular smooth muscle.Cell Calcium, vol. 46, no. 1, July 2009, pp. 65–72. Pubmed, doi:10.1016/j.ceca.2009.05.001.
Journal cover image

Published In

Cell Calcium

DOI

EISSN

1532-1991

Publication Date

July 2009

Volume

46

Issue

1

Start / End Page

65 / 72

Location

Netherlands

Related Subject Headings

  • rho-Associated Kinases
  • Rabbits
  • Pyrrolidines
  • Pyrones
  • Protein Kinase C
  • Potassium Chloride
  • Phospholipases A2, Calcium-Independent
  • Phenylephrine
  • Naphthalenes
  • Myosin-Light-Chain Kinase