Skip to main content
Erschienen in: Sleep and Breathing 4/2022

13.01.2022 | Sleep Breathing Physiology and Disorders • Original Article

The reduced contraction capacity of palatopharyngeal muscle in OSAHS is related to the decreased intra-cellular [Ca2+] mediated by low RyR1 and DHPRα1s expression

Erschienen in: Sleep and Breathing | Ausgabe 4/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To aim of the study was to explore the possible mechanisms for the decreased contraction capacity of the palatopharyngeal muscle in cases with obstructive sleep apnea hypopnea syndrome (OSAHS).

Methods

Palatopharyngeal muscle specimens from patients with OSAHS were taken as the case group. Palatopharyngeal muscle tissue by surgical removal of oropharyngeal malignant tumors was used as a control cohort. The palatopharyngeal muscle contraction capacity was measured by assessing diaphragm peak-twitching force / cross-sectional area (Pt/CSA), fatigue index (FI) twitch tension, and force per cross-sectional area (Force/CSA). Myofibril and sarcoplasmic reticulum (SR) ultra-structures were observed by electron microscopy. The intra-cellular calcium concentration was measured by fluorescence spectrophotometry. DHPRα1s and RyR1 expression profiles were probed through RT-qPCR and Western blot, and the colocalization of them was determined by immunofluorescence.

Results

In comparison with the control cohort, the OSAHS cohort demonstrated decreased Pt/CSA (P < 0.01), FI twitch tension (P < 0.01), together with contraction capacity (P < 0.01). This cohort also had lower intra-cellular [Ca2+] of palatopharyngeal muscle cells with abnormal ultrastructure of sarcoplasmic reticulum (SR) (P < 0.01). In addition, transcriptomic (P < 0.01) and proteomic expression (P < 0.01) for RyR1 and DHPRα1s were markedly reduced within OSAHS cohort, although the degree of colocalization of them was not altered.

Conclusion

RyR1 and DHPRα1s downregulation may disrupt intra-cellular [Ca2+] homeostasis and subsequently decrease the palatopharyngeal muscle contraction capacity in patients with OSAHS, thus providing a novel insight into the pathogenesis of OSAHS.
Literatur
1.
Zurück zum Zitat Lee JJ, Sundar KM (2021) Evaluation and Management of Adults with Obstructive Sleep Apnea Syndrome. Lung 199(2):87–101CrossRefPubMed Lee JJ, Sundar KM (2021) Evaluation and Management of Adults with Obstructive Sleep Apnea Syndrome. Lung 199(2):87–101CrossRefPubMed
2.
Zurück zum Zitat Mohit A, Shrivastava P (2021) Chand, Molecular determinants of obstructive sleep apnea. Sleep Med 80:105–112CrossRefPubMed Mohit A, Shrivastava P (2021) Chand, Molecular determinants of obstructive sleep apnea. Sleep Med 80:105–112CrossRefPubMed
3.
Zurück zum Zitat Ko CY, Liu QQ, Su HZ, Zhang HP, Fan JM, Yang JH, Hu AK, Liu YQ, Chou D, Zeng YM (2019) Gut microbiota in obstructive sleep apnea-hypopnea syndrome: disease-related dysbiosis and metabolic comorbidities. Clin Sci (Lond) 133(7):905–917CrossRef Ko CY, Liu QQ, Su HZ, Zhang HP, Fan JM, Yang JH, Hu AK, Liu YQ, Chou D, Zeng YM (2019) Gut microbiota in obstructive sleep apnea-hypopnea syndrome: disease-related dysbiosis and metabolic comorbidities. Clin Sci (Lond) 133(7):905–917CrossRef
4.
Zurück zum Zitat Garg RK, Afifi AM, Sanchez R, King TW (2016) Obstructive Sleep Apnea in Adults: The Role of Upper Airway and Facial Skeletal Surgery. Plast Reconstr Surg 138(4):889–898CrossRefPubMed Garg RK, Afifi AM, Sanchez R, King TW (2016) Obstructive Sleep Apnea in Adults: The Role of Upper Airway and Facial Skeletal Surgery. Plast Reconstr Surg 138(4):889–898CrossRefPubMed
5.
Zurück zum Zitat Zhan X, Li L, Wu C, Chitguppi C, Huntley C, Fang F, Wei Y (2019) Effect of uvulopalatopharyngoplasty (UPPP) on atherosclerosis and cardiac functioning in obstructive sleep apnea patients. Acta Otolaryngol 139(9):793–797CrossRefPubMed Zhan X, Li L, Wu C, Chitguppi C, Huntley C, Fang F, Wei Y (2019) Effect of uvulopalatopharyngoplasty (UPPP) on atherosclerosis and cardiac functioning in obstructive sleep apnea patients. Acta Otolaryngol 139(9):793–797CrossRefPubMed
6.
Zurück zum Zitat Eshima H, Poole DC, Kano Y (2014) In vivo calcium regulation in diabetic skeletal muscle. Cell Calcium 56(5):381–389CrossRefPubMed Eshima H, Poole DC, Kano Y (2014) In vivo calcium regulation in diabetic skeletal muscle. Cell Calcium 56(5):381–389CrossRefPubMed
7.
Zurück zum Zitat Allen DG, Lamb GD, Westerblad H (2008) Impaired calcium release during fatigue. J Appl Physiol (1985) 104(1):296–305CrossRef Allen DG, Lamb GD, Westerblad H (2008) Impaired calcium release during fatigue. J Appl Physiol (1985) 104(1):296–305CrossRef
8.
Zurück zum Zitat Luo Y, Rall JA (2006) Regulation of contraction kinetics in skinned skeletal muscle fibers by calcium and troponin C. Arch Biochem Biophys 456(2):119–126CrossRefPubMed Luo Y, Rall JA (2006) Regulation of contraction kinetics in skinned skeletal muscle fibers by calcium and troponin C. Arch Biochem Biophys 456(2):119–126CrossRefPubMed
9.
Zurück zum Zitat Kushnir A, Wajsberg B, Marks AR (2018) Ryanodine receptor dysfunction in human disorders. Biochim Biophys Acta Mol Cell Res 1865(11 Pt B):1687–1697CrossRefPubMed Kushnir A, Wajsberg B, Marks AR (2018) Ryanodine receptor dysfunction in human disorders. Biochim Biophys Acta Mol Cell Res 1865(11 Pt B):1687–1697CrossRefPubMed
10.
Zurück zum Zitat Clancy JS, Takeshima H, Hamilton SL, Reid MB (1999) Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3. Am J Physiol 277(4 Pt 2):R1205–R1209PubMed Clancy JS, Takeshima H, Hamilton SL, Reid MB (1999) Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3. Am J Physiol 277(4 Pt 2):R1205–R1209PubMed
11.
Zurück zum Zitat Fill M, Copello JA (2002) Ryanodine receptor calcium release channels. Physiol Rev 82(4):893–922CrossRefPubMed Fill M, Copello JA (2002) Ryanodine receptor calcium release channels. Physiol Rev 82(4):893–922CrossRefPubMed
12.
Zurück zum Zitat Ogawa Y, Kurebayashi N, Murayama T (2000) Putative roles of type 3 ryanodine receptor isoforms (RyR3). Trends Cardiovasc Med 10(2):65–70CrossRefPubMed Ogawa Y, Kurebayashi N, Murayama T (2000) Putative roles of type 3 ryanodine receptor isoforms (RyR3). Trends Cardiovasc Med 10(2):65–70CrossRefPubMed
13.
Zurück zum Zitat Dulhunty AF, Wei-LaPierre L, Casarotto MG, Beard NA (2017) Core skeletal muscle ryanodine receptor calcium release complex. Clin Exp Pharmacol Physiol 44(1):3–12CrossRefPubMed Dulhunty AF, Wei-LaPierre L, Casarotto MG, Beard NA (2017) Core skeletal muscle ryanodine receptor calcium release complex. Clin Exp Pharmacol Physiol 44(1):3–12CrossRefPubMed
14.
Zurück zum Zitat Wang MM, Hao LY, Guo F, Zhong B, Zhong XM, Yuan J, Hao YF, Zhao S, Sun XF, Lei M, Jiao GY (2017) Decreased intracellular [Ca(2+) ] coincides with reduced expression of Dhpralpha1s, RyR1, and diaphragmatic dysfunction in a rat model of sepsis. Muscle Nerve 56(6):1128–1136CrossRefPubMed Wang MM, Hao LY, Guo F, Zhong B, Zhong XM, Yuan J, Hao YF, Zhao S, Sun XF, Lei M, Jiao GY (2017) Decreased intracellular [Ca(2+) ] coincides with reduced expression of Dhpralpha1s, RyR1, and diaphragmatic dysfunction in a rat model of sepsis. Muscle Nerve 56(6):1128–1136CrossRefPubMed
15.
Zurück zum Zitat Jiao GY, Hao LY, Gao CE, Chen L, Sun XF, Yang HL, Li Y, Dai YN (2013) Reduced DHPRalpha1S and RyR1 expression levels are associated with diaphragm contractile dysfunction during sepsis. Muscle Nerve 48(5):745–751CrossRefPubMed Jiao GY, Hao LY, Gao CE, Chen L, Sun XF, Yang HL, Li Y, Dai YN (2013) Reduced DHPRalpha1S and RyR1 expression levels are associated with diaphragm contractile dysfunction during sepsis. Muscle Nerve 48(5):745–751CrossRefPubMed
16.
Zurück zum Zitat Du K, Liu M, Zhong X, Yao W, Xiao Q, Wen Q, Yang B, Wei M (2018) Epigallocatechin Gallate Reduces Amyloid beta-Induced Neurotoxicity via Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis. Mol Nutr Food Res 62(8):e1700890CrossRefPubMed Du K, Liu M, Zhong X, Yao W, Xiao Q, Wen Q, Yang B, Wei M (2018) Epigallocatechin Gallate Reduces Amyloid beta-Induced Neurotoxicity via Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis. Mol Nutr Food Res 62(8):e1700890CrossRefPubMed
17.
Zurück zum Zitat Tangel DJ, Mezzanotte WS, White DP (1991) Influence of sleep on tensor palatini EMG and upper airway resistance in normal men. J Appl Physiol (1985) 70(6):2574–81CrossRef Tangel DJ, Mezzanotte WS, White DP (1991) Influence of sleep on tensor palatini EMG and upper airway resistance in normal men. J Appl Physiol (1985) 70(6):2574–81CrossRef
18.
Zurück zum Zitat Malhotra A, Fogel RB, Edwards JK, Shea SA, White DP (2000) Local mechanisms drive genioglossus activation in obstructive sleep apnea. Am J Respir Crit Care Med 161(5):1746–1749CrossRefPubMed Malhotra A, Fogel RB, Edwards JK, Shea SA, White DP (2000) Local mechanisms drive genioglossus activation in obstructive sleep apnea. Am J Respir Crit Care Med 161(5):1746–1749CrossRefPubMed
19.
Zurück zum Zitat Dong J, Niu X, Chen X (2020) Injury and Apoptosis in the Palatopharyngeal Muscle in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome. Med Sci Monit 26:e919501CrossRefPubMedPubMedCentral Dong J, Niu X, Chen X (2020) Injury and Apoptosis in the Palatopharyngeal Muscle in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome. Med Sci Monit 26:e919501CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Boyd JH, Petrof BJ, Hamid Q, Fraser R, Kimoff RJ (2004) Upper airway muscle inflammation and denervation changes in obstructive sleep apnea. Am J Respir Crit Care Med 170(5):541–546CrossRefPubMed Boyd JH, Petrof BJ, Hamid Q, Fraser R, Kimoff RJ (2004) Upper airway muscle inflammation and denervation changes in obstructive sleep apnea. Am J Respir Crit Care Med 170(5):541–546CrossRefPubMed
21.
Zurück zum Zitat Friberg D, Ansved T, Borg K, Carlsson-Nordlander B, Larsson H, Svanborg E (1998) Histological indications of a progressive snorers disease in an upper airway muscle. Am J Respir Crit Care Med 157(2):586–593CrossRefPubMed Friberg D, Ansved T, Borg K, Carlsson-Nordlander B, Larsson H, Svanborg E (1998) Histological indications of a progressive snorers disease in an upper airway muscle. Am J Respir Crit Care Med 157(2):586–593CrossRefPubMed
22.
Zurück zum Zitat Series F, Simoneau JA, St Pierre S (2000) Muscle fiber area distribution of musculus uvulae in obstructive sleep apnea and non-apneic snorers. Int J Obes Relat Metab Disord 24(4):410–5CrossRefPubMed Series F, Simoneau JA, St Pierre S (2000) Muscle fiber area distribution of musculus uvulae in obstructive sleep apnea and non-apneic snorers. Int J Obes Relat Metab Disord 24(4):410–5CrossRefPubMed
23.
Zurück zum Zitat Lynch PJ, Tong J, Lehane M, Mallet A, Giblin L, Heffron JJ, Vaughan P, Zafra G, MacLennan DH, McCarthy TV (1999) A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease. Proc Natl Acad Sci U S A 96(7):4164–4169CrossRefPubMedPubMedCentral Lynch PJ, Tong J, Lehane M, Mallet A, Giblin L, Heffron JJ, Vaughan P, Zafra G, MacLennan DH, McCarthy TV (1999) A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease. Proc Natl Acad Sci U S A 96(7):4164–4169CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Avila G, Dirksen RT (2001) Functional effects of central core disease mutations in the cytoplasmic region of the skeletal muscle ryanodine receptor. J Gen Physiol 118(3):277–290CrossRefPubMedPubMedCentral Avila G, Dirksen RT (2001) Functional effects of central core disease mutations in the cytoplasmic region of the skeletal muscle ryanodine receptor. J Gen Physiol 118(3):277–290CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Andersson DC, Meli AC, Reiken S, Betzenhauser MJ, Umanskaya A, Shiomi T, D’Armiento J, Marks AR (2012) Leaky ryanodine receptors in beta-sarcoglycan deficient mice: a potential common defect in muscular dystrophy. Skelet Muscle 2(1):9CrossRefPubMedPubMedCentral Andersson DC, Meli AC, Reiken S, Betzenhauser MJ, Umanskaya A, Shiomi T, D’Armiento J, Marks AR (2012) Leaky ryanodine receptors in beta-sarcoglycan deficient mice: a potential common defect in muscular dystrophy. Skelet Muscle 2(1):9CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Bellinger AM, Reiken S, Carlson C, Mongillo M, Liu X, Rothman L, Matecki S, Lacampagne A, Marks AR (2009) Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle. Nat Med 15(3):325–330CrossRefPubMedPubMedCentral Bellinger AM, Reiken S, Carlson C, Mongillo M, Liu X, Rothman L, Matecki S, Lacampagne A, Marks AR (2009) Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle. Nat Med 15(3):325–330CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Cheng W, Altafaj X, Ronjat M, Coronado R (2005) Interaction between the dihydropyridine receptor Ca2+ channel beta-subunit and ryanodine receptor type 1 strengthens excitation-contraction coupling. Proc Natl Acad Sci U S A 102(52):19225–19230CrossRefPubMedPubMedCentral Cheng W, Altafaj X, Ronjat M, Coronado R (2005) Interaction between the dihydropyridine receptor Ca2+ channel beta-subunit and ryanodine receptor type 1 strengthens excitation-contraction coupling. Proc Natl Acad Sci U S A 102(52):19225–19230CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat FleuryCurado T, Pho H, Freire C, Amorim MR, Bonaventura J, Kim LJ, Lee R, Cabassa ME, Streeter SR, Branco LG, Sennes LU, Fishbein K, Spencer RG, Schwartz AR, Brennick MJ, Michaelides M, Fuller DD, Polotsky VY (2021) Designer Receptors Exclusively Activated by Designer Drugs Approach to Treatment of Sleep-disordered Breathing. Am J Respir Crit Care Med 203(1):102–110CrossRef FleuryCurado T, Pho H, Freire C, Amorim MR, Bonaventura J, Kim LJ, Lee R, Cabassa ME, Streeter SR, Branco LG, Sennes LU, Fishbein K, Spencer RG, Schwartz AR, Brennick MJ, Michaelides M, Fuller DD, Polotsky VY (2021) Designer Receptors Exclusively Activated by Designer Drugs Approach to Treatment of Sleep-disordered Breathing. Am J Respir Crit Care Med 203(1):102–110CrossRef
30.
Zurück zum Zitat Perger E, Taranto-Montemurro L (2021) Upper airway muscles: influence on obstructive sleep apnoea pathophysiology and pharmacological and technical treatment options. Curr Opin Pulm Med 27(6):505–513CrossRefPubMed Perger E, Taranto-Montemurro L (2021) Upper airway muscles: influence on obstructive sleep apnoea pathophysiology and pharmacological and technical treatment options. Curr Opin Pulm Med 27(6):505–513CrossRefPubMed
Metadaten
Titel
The reduced contraction capacity of palatopharyngeal muscle in OSAHS is related to the decreased intra-cellular [Ca2+] mediated by low RyR1 and DHPRα1s expression
Publikationsdatum
13.01.2022
Erschienen in
Sleep and Breathing / Ausgabe 4/2022
Print ISSN: 1520-9512
Elektronische ISSN: 1522-1709
DOI
https://doi.org/10.1007/s11325-022-02562-w

Weitere Artikel der Ausgabe 4/2022

Sleep and Breathing 4/2022 Zur Ausgabe

Sleep Breathing Physiology and Disorders • Original Article

The frequency of obstructive sleep apnea in patients with primary Sjogren’s syndrome

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.