Ca<sup>2+</sup>oscillations, Ca<sup>2+</sup>sensitization, and contraction activated by protein kinase C in small airway smooth muscle

Mukherjee, Subhajit; Trice, Jacquelyn; Shinde, Paurvi; Willis, Ray E.; Pressley, Thomas A.; Perez‐Zoghbi, Jose F.

doi:10.1083/jcb2003oia7

Cited by 3 publications

(9 citation statements)

References 32 publications

(48 reference statements)

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“…; Eto, ; Mukherjee et al . ; Eto & Kitazawa, ). MYPT1 phosphorylation may also mediate Ca 2+ sensitization responses.…”

Section: Introductionmentioning

confidence: 99%

“…Different signalling pathways are proposed to inhibit MLCP activity, thereby increasing RLC phosphorylation without changing elevated [Ca 2+ ] i (Ca 2+ sensitization). Ca 2+ sensitization in intact smooth muscle tissues may be mediated, in part, by phosphorylation of a small inhibitor protein CPI-17 (PKC-potentiated protein phosphatase 1 inhibitor protein of 17 kDa) at T38 by protein kinase C (Sakai et al 2005;Eto, 2009;Mukherjee et al 2013;Eto & Kitazawa, 2017). MYPT1 phosphorylation may also mediate Ca 2+ sensitization responses.…”

Section: Introductionmentioning

confidence: 99%

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Physiological vs. pharmacological signalling to myosin phosphorylation in airway smooth muscle

Gao

Tsai

Chang

et al. 2017

The Journal of Physiology

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Key points Smooth muscle myosin regulatory light chain (RLC) is phosphorylated by Ca2+/calmodulin‐dependent myosin light chain kinase and dephosphorylated by myosin light chain phosphatase (MLCP). Tracheal smooth muscle contains significant amounts of myosin binding subunit 85 (MBS85), another myosin phosphatase targeting subunit (MYPT) family member, in addition to MLCP regulatory subunit MYPT1. Concentration/temporal responses to carbachol demonstrated similar sensitivities for bovine tracheal force development and phosphorylation of RLC, MYPT1, MBS85 and paxillin. Electrical field stimulation releases ACh from nerves to increase RLC phosphorylation but not MYPT1 or MBS85 phosphorylation. Thus, nerve‐mediated muscarinic responses in signalling modules acting on RLC phosphorylation are different from pharmacological responses with bath added agonist. The conditional knockout of MYPT1 or the knock‐in mutation T853A in mice had no effect on muscarinic force responses in isolated tracheal tissues. MLCP activity may arise from functionally shared roles between MYPT1 and MBS85, resulting in minimal effects of MYPT1 knockout on contraction. Abstract Ca2+/calmodulin activation of myosin light chain kinase (MLCK) initiates myosin regulatory light chain (RLC) phosphorylation for smooth muscle contraction with subsequent dephosphorylation for relaxation by myosin light chain phosphatase (MLCP) containing regulatory (MYPT1) and catalytic (PP1cδ) subunits. RLC phosphorylation‐dependent force development is regulated by distinct signalling modules involving protein phosphorylations. We investigated responses to cholinergic agonist treatment vs. neurostimulation by electric field stimulation (EFS) in bovine tracheal smooth muscle. Concentration/temporal responses to carbachol demonstrated tight coupling between force development and RLC phosphorylation but sensitivity differences in MLCK, MYPT1 T853, MYPT1 T696, myosin binding subunit 85 (MBS85), paxillin and CPI‐17 (PKC‐potentiated protein phosphatase 1 inhibitor protein of 17 kDa) phosphorylations. EFS increased force and phosphorylation of RLC, CPI‐17 and MLCK. In the presence of the cholinesterase inhibitor neostigmine, EFS led to an additional increase in phosphorylation of MYPT1 T853, MYPT1 T696, MBS85 and paxillin. Thus, there were distinct pharmacological vs. physiological responses in signalling modules acting on RLC phosphorylation and force responses, probably related to degenerate G protein signalling networks. Studies with genetically modified mice were performed. Expression of another MYPT1 family member, MBS85, was enriched in mouse, as well as bovine tracheal smooth muscle. Carbachol concentration/temporal‐force responses were similar in trachea from MYPT1SM+/+, MYPT1SM‐/− and the knock‐in mutant mice containing nonphosphorylatable MYPT1 T853A with no differences in RLC phosphorylation. Thus, MYPT1 T853 phosphorylation was not necessary for regulation of RLC phosphorylation in tonic airway smooth muscle. Furthermore, MLCP activity may arise from functionally...

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“…; Eto, ; Mukherjee et al . ; Eto & Kitazawa, ). MYPT1 phosphorylation may also mediate Ca 2+ sensitization responses.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Physiological vs. pharmacological signalling to myosin phosphorylation in airway smooth muscle

Gao

Tsai

Chang

et al. 2017

The Journal of Physiology

View full text Add to dashboard Cite

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“…This ratio is influenced by the frequency of Ca 2+ oscillations and the degree of Ca 2+ sensitivity. Contractile agonists that stimulate airway smooth muscle and produce Ca 2+ oscillations include substances that promote membrane depolarization (e.g., KCl) and ligands of G protein–coupled receptors that initiate signaling via either the G q/11 or the G 12/13 signaling pathways (Mukherjee et al, 2013). Membrane depolarization (with KCl) has been reported to stimulate Ca 2+ entry into airway SMCs via L-type voltage-gated calcium channels; this elevates free intracellular Ca 2+ concentration ([Ca 2+ ] i ) and leads to overloading of the SR Ca 2+ stores and consequently to release of Ca 2+ from the SR into the cytosol.…”

mentioning

confidence: 99%

“…Mukherjee et al (2013) addressed an elusive issue: a possible role for PKC, which is activated by phorbol esters, and Ca 2+ oscillations in tuning excitation–contraction coupling in airway smooth muscle. To do this, they used the mouse lung slice preparation.…”

mentioning

confidence: 99%

“…Mukherjee et al (2013) used low magnification (10×) phase-contrast microscopy to obtain time-lapse (0.5-Hz) images of lung slices and monitored changes in the cross-sectional area of airway lumens in response to perfusion with various contractile agonists, PKC activators, and PKC antagonists. Additionally, they used confocal microscopy to examine lung slices loaded with the calcium indicator dye Oregon green, permitting visualization of Ca 2+ signaling within individual airway SMCs.…”

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confidence: 99%

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A Ca2+- and PKC-driven regulatory network in airway smooth muscle

Dixon

Santana

2013

Journal of General Physiology

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Physiology of Airway Smooth Muscle Contraction: An Overview

Ouédraogo¹

2014

J Pulm Respir Med

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Bronchial reactivity is a physiological property of healthy airways to develop a moderate airway obstruction in response to various non-specific stimuli, which is altered in several pulmonary diseases. The active effector of airway reactivity is airway smooth muscle (ASM). The contractile status of airway smooth muscle is under the control of many extracellular messengers acting on specific membrane receptors. Binding of the contractile messengers to their specific membrane receptors increases cytosolic Ca 2+ concentration ([Ca 2+ ]i). The shape of the resulting calcium signal is sensed by the contractile apparatus and hence determines the pattern of the contractile response. Agonists can also modify the sensitivity of the contractile apparatus to calcium, via phosphorylation and dephosphorylation of a network of regulatory proteins. These mechanisms can be altered in several respiratory diseases such and COPD, asthma, or exposure to air pollutants, leading to hyperreactivity, which can be pharmacologically controlled by drugs acting on the mechanisms of ASM contraction. The article describes the major intracellular mechanisms responsible for the excitation-contraction coupling in airway smooth muscle cell.

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Ca²⁺oscillations, Ca²⁺sensitization, and contraction activated by protein kinase C in small airway smooth muscle

Cited by 3 publications

References 32 publications

Physiological vs. pharmacological signalling to myosin phosphorylation in airway smooth muscle

Physiological vs. pharmacological signalling to myosin phosphorylation in airway smooth muscle

A Ca2+- and PKC-driven regulatory network in airway smooth muscle

Physiology of Airway Smooth Muscle Contraction: An Overview

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Ca2+oscillations, Ca2+sensitization, and contraction activated by protein kinase C in small airway smooth muscle

Cited by 3 publications

References 32 publications

Physiological vs. pharmacological signalling to myosin phosphorylation in airway smooth muscle

Physiological vs. pharmacological signalling to myosin phosphorylation in airway smooth muscle

A Ca2+- and PKC-driven regulatory network in airway smooth muscle

Physiology of Airway Smooth Muscle Contraction: An Overview

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Ca²⁺oscillations, Ca²⁺sensitization, and contraction activated by protein kinase C in small airway smooth muscle