Accessible Unlicensed Requires Authentication Published by De Gruyter January 8, 2018

Calcium sensitization mechanisms in detrusor smooth muscles

Irfan Anjum

Abstract

The contraction of detrusor smooth muscles depends on the increase in intracellular calcium. The influx of calcium from the plasma membrane calcium channels and calcium release from the sarcoplasmic reticulum give rise to intracellular calcium. Under the pathophysiological conditions, the increased sensitivity of regulatory and contractile proteins to calcium also plays an important role in maintaining the spontaneous detrusor smooth muscle activity. Many proteins have been identified to play a role in calcium sensitization. Both the protein kinase C (PKC) and Rho-kinase (ROCK) signaling pathways are responsible for the induction of calcium sensitization in the detrusor smooth muscles. The balance between the myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) regulates the intracellular calcium-contractile force relationship. The inhibition of MLCP by PKC-mediated phosphatase inhibitor (CPI-17) and myosin phosphatase target subunit (MYPT-1) phosphorylation by both the PKC and ROCK are responsible for calcium sensitization in the detrusor smooth muscles. However, the ROCK pathway predominantly participates in the calcium sensitization induction under pathophysiological situations. Many kinases are well known nowadays to play a role in calcium sensitization. This review aims to enlighten the current understanding of the regulatory mechanisms of calcium sensitization with special reference to the PKC and ROCK pathways in the detrusor smooth muscles. It will also aid in the development of new pharmacological strategies to prevent and treat bladder diseases.


Corresponding author: Irfan Anjum, Research Assistant, Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, 06100 Sihhiye, Ankara, Turkey, Phone: +90 312 3052131, +90-5545988354

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2017-5-9
Accepted: 2017-10-12
Published Online: 2018-1-8
Published in Print: 2018-6-27

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