DOI QR코드

DOI QR Code

Calcium Signaling in Salivary Secretion

  • Kim, Jin Man (Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Lee, Sang-Woo (Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Park, Kyungpyo (Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University)
  • Received : 2017.10.27
  • Accepted : 2017.12.19
  • Published : 2017.12.30

Abstract

Calcium has versatile roles in diverse physiological functions. Among these functions, intracellular $Ca^{2+}$ plays a key role during the secretion of salivary glands. In this review, we introduce the diverse cellular components involved in the saliva secretion and related dynamic intracellular $Ca^{2+}$ signals. Calcium acts as a critical second messenger for channel activation, protein translocation, and volume regulation, which are essential events for achieving the salivary secretion. In the secretory process, $Ca^{2+}$ activates $K^+$ and $Cl^-$ channels to transport water and electrolyte constituting whole saliva. We also focus on the $Ca^{2+}$ signals from intracellular stores with discussion about detailed molecular mechanism underlying the generation of characteristic $Ca^{2+}$ patterns. In particular, inositol triphosphate signal is a main trigger for inducing $Ca^{2+}$ signals required for the salivary gland functions. The biphasic response of inositol triphosphate receptor and $Ca^{2+}$ pumps generate a self-limiting pattern of $Ca^{2+}$ efflux, resulting in $Ca^{2+}$ oscillations. The regenerative $Ca^{2+}$ oscillations have been detected in salivary gland cells, but the exact mechanism and function of the signals need to be elucidated. In future, we expect that further investigations will be performed toward better understanding of the spatiotemporal role of $Ca^{2+}$ signals in regulating salivary secretion.

Keywords

References

  1. Narhi TO, Meurman JH, Ainamo A. Xerostomia and hyposalivation: causes, consequences and treatment in the elderly. Drugs Aging. 1999; 15: 103-16. https://doi.org/10.2165/00002512-199915020-00004
  2. Petersen OH. Stimulus-secretion coupling: cytoplasmic calcium signals and the control of ion channels in exocrine acinar cells. J Physiol. 1992; 448: 1-51. https://doi.org/10.1113/jphysiol.1992.sp019028
  3. Park KP, Beck JS, Douglas IJ, Brown PD. Ca(2+)-activated K+ channels are involved in regulatory volume decrease in acinar cells isolated from the rat lacrimal gland. J Membr Biol. 1994; 141: 193-201.
  4. Catalan MA, Pena-Munzenmayer G, Melvin JE. Ca2+-dependent K+ channels in exocrine salivary glands. Cell Calcium. 2014; 55: 362-8. https://doi.org/10.1016/j.ceca.2014.01.005
  5. Cho SM, Piao ZG, Kim YB, Kim JS, Park K. Characterization of intermediate conductance K+ channels in submandibular gland acinar cells. Korean J Physiol Pharmacol. 2002; 6: 305-9.
  6. Park K, Case RM, Brown PD. Identification and regulation of K+ and Cl- channels in human parotid acinar cells. Arch Oral Biol. 2001; 46: 801-10. https://doi.org/10.1016/S0003-9969(01)00047-4
  7. Park K, Majid A. Expression of volume-activated anion channels in exocrine acinar cells. J Korean Med Sci. 2000; 15 Suppl: S61-2. https://doi.org/10.3346/jkms.2000.15.S.S61
  8. Majid A, Brown PD, Best L, Park K. Expression of volume-sensitive Cl(-) channels and ClC-3 in acinar cells isolated from the rat lacrimal gland and submandibular salivary gland. J Physiol. 2001; 534: 409-21. https://doi.org/10.1111/j.1469-7793.2001.00409.x
  9. Park K, Brown PD. Intracellular pH modulates the activity of chloride channels in isolated lacrimal gland acinar cells. Am J Physiol. 1995; 268: C647-50. https://doi.org/10.1152/ajpcell.1995.268.3.C647
  10. Li J, Lee S, Choi SY, Lee SJ, Oh SB, Lee JH, Chung SC, Kim JS, Lee JH, Park K. Effects of pilocarpine on the secretory acinar cells in human submandibular glands. Life Sci. 2006; 79: 2441-7. https://doi.org/10.1016/j.lfs.2006.08.006
  11. Lee K, Choi S, Choi LM, Lee J, Kim JH, Chung G, Lee G, Choi SY, Park K. Desipramine inhibits salivary Ca(2+) signaling and aquaporin translocation. Oral Dis. 2015; 21: 530-5. https://doi.org/10.1111/odi.12317
  12. Park K, Lee S, Elliott AC, Kim JS, Lee JH. Swellinginduced Ca2+ release from intracellular calcium stores in rat submandibular gland acinar cells. J Membr Biol. 2002; 186: 165-76. https://doi.org/10.1007/s00232-001-0144-8
  13. Verkhratsky A. Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons. Physiol Rev. 2005; 85: 201-79. https://doi.org/10.1152/physrev.00004.2004
  14. Berridge MJ. Inositol trisphosphate and calcium signalling. Nature. 1993; 361: 315-25. https://doi.org/10.1038/361315a0
  15. Clapham DE. Calcium signaling. Cell. 2007; 131: 1047-58. https://doi.org/10.1016/j.cell.2007.11.028
  16. Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol. 2000; 1: 11-21.
  17. Putney JW Jr. Capacitative calcium entry: sensing the calcium stores. J Cell Biol. 2005; 169: 381-2. https://doi.org/10.1083/jcb.200503161
  18. Collin T, Marty A, Llano I. Presynaptic calcium stores and synaptic transmission. Curr Opin Neurobiol. 2005; 15: 275-81. https://doi.org/10.1016/j.conb.2005.05.003
  19. Rose CR, Konnerth A. Stores not just for storage. intracellular calcium release and synaptic plasticity. Neuron. 2001; 31: 519-22. https://doi.org/10.1016/S0896-6273(01)00402-0
  20. Endo M. Calcium-induced calcium release in skeletal muscle. Physiol Rev. 2009; 89: 1153-76. https://doi.org/10.1152/physrev.00040.2008
  21. Tse FW, Tse A, Hille B, Horstmann H, Almers W. Local Ca2+ release from internal stores controls exocytosis in pituitary gonadotrophs. Neuron. 1997; 18: 121-32. https://doi.org/10.1016/S0896-6273(01)80051-9
  22. Case RM, Clausen T. The relationship between calcium exchange and enzyme secretion in the isolated rat pancreas. J Physiol. 1973; 235: 75-102. https://doi.org/10.1113/jphysiol.1973.sp010379
  23. Eglen RM, Choppin A, Dillon MP, Hegde S. Muscarinic receptor ligands and their therapeutic potential. Curr Opin Chem Biol. 1999; 3: 426-32. https://doi.org/10.1016/S1367-5931(99)80063-5
  24. Gautam D, Heard TS, Cui Y, Miller G, Bloodworth L, Wess J. Cholinergic stimulation of salivary secretion studied with M1 and M3 muscarinic receptor single- and double-knockout mice. Mol Pharmacol. 2004; 66: 260-7. https://doi.org/10.1124/mol.66.2.260
  25. Abrams P, Andersson KE, Buccafusco JJ, Chapple C, de Groat WC, Fryer AD, Kay G, Laties A, Nathanson NM, Pasricha PJ, Wein AJ. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol. 2006; 148: 565-78. https://doi.org/10.1038/sj.bjp.0706780
  26. Kim N, Shin Y, Choi S, Namkoong E, Kim M, Lee J, Song Y, Park K. Effect of antimuscarinic autoantibodies in primary Sjogren's syndrome. J Dent Res. 2015; 94: 722-8. https://doi.org/10.1177/0022034515577813
  27. Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, Park SP, Lee J, Lee B, Kim BM, Raouf R, Shin YK, Oh U. TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature. 2008; 455: 1210-5. https://doi.org/10.1038/nature07313
  28. Melvin JE, Yule D, Shuttleworth T, Begenisich T. Regulation of fluid and electrolyte secretion in salivary gland acinar cells. Annu Rev Physiol. 2005; 67: 445-69. https://doi.org/10.1146/annurev.physiol.67.041703.084745
  29. Shin YH, Kim JM, Park K. The effect of capsaicin on salivary gland dysfunction. Molecules. 2016; 21. doi: 10.3390/molecules21070835.
  30. Lee MG, Xu X, Zeng W, Diaz J, Wojcikiewicz RJ, Kuo TH, Wuytack F, Racymaekers L, Muallem S. Polarized expression of Ca2+ channels in pancreatic and salivary gland cells. Correlation with initiation and propagation of [Ca2+]i waves. J Biol Chem. 1997; 272: 15765-70. https://doi.org/10.1074/jbc.272.25.15765
  31. Zhang X, Wen J, Bidasee KR, Besch HR Jr, Wojcikiewicz RJ, Lee B, Rubin RP. Ryanodine and inositol trisphosphate receptors are differentially distributed and expressed in rat parotid gland. Biochem J. 1999; 340: 519-27. https://doi.org/10.1042/bj3400519
  32. Kim JM, Choi S, Park K. TRPM7 is involved in volume regulation in salivary glands. J Dent Res. 2017; 96: 1044-50. https://doi.org/10.1177/0022034517708766
  33. Takayama Y, Shibasaki K, Suzuki Y, Yamanaka A, Tominaga M. Modulation of water efflux through functional interaction between TRPV4 and TMEM16A/anoctamin 1. FASEB J. 2014; 28: 2238-48. https://doi.org/10.1096/fj.13-243436
  34. Franzini-Armstrong C, Protasi F, Ramesh V. Shape, size, and distribution of Ca(2+) release units and couplons in skeletal and cardiac muscles. Biophys J. 1999; 77: 1528-39. https://doi.org/10.1016/S0006-3495(99)77000-1
  35. Parkash J, Asotra K. Calcium oscillations and waves in cells. Adv Exp Med Biol. 2012; 740: 521-9.
  36. Cheng H, Lederer WJ. Calcium sparks. Physiol Rev. 2008; 88: 1491-545. https://doi.org/10.1152/physrev.00030.2007
  37. Newman EA, Zahs KR. Calcium waves in retinal glial cells. Science. 1997; 275: 844-7. https://doi.org/10.1126/science.275.5301.844
  38. Dupont G, Combettes L, Bird GS, Putney JW. Calcium oscillations. Cold Spring Harb Perspect Biol. 2011; 3. doi: 10.1101/cshperspect.a004226.
  39. Endo M, Tanaka M, Ogawa Y. Calcium induced release of calcium from the sarcoplasmic reticulum of skinned skeletal muscle fibres. Nature. 1970; 228: 34-6. https://doi.org/10.1038/228034a0
  40. Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol. 2003; 4: 517-29.
  41. Uhlen P, Fritz N. Biochemistry of calcium oscillations. Biochem Biophys Res Commun. 2010; 396: 28-32. https://doi.org/10.1016/j.bbrc.2010.02.117
  42. Campbell K, Swann K. Ca2+ oscillations stimulate an ATP increase during fertilization of mouse eggs. Dev Biol. 2006; 298: 225-33. https://doi.org/10.1016/j.ydbio.2006.06.032
  43. Estrada M, Uhlen P, Ehrlich BE. Ca2+ oscillations induced by testosterone enhance neurite outgrowth. J Cell Sci. 2006; 119: 733-43. https://doi.org/10.1242/jcs.02775
  44. Hanley PJ, Musset B, Renigunta V, Limberg SH, Dalpke AH, Sus R, Heeg KM, Preisig-Muller R, Daut J. Extracellular ATP induces oscillations of intracellular Ca2+ and membrane potential and promotes transcription of IL-6 in macrophages. Proc Natl Acad Sci U S A. 2004; 101: 9479-84. https://doi.org/10.1073/pnas.0400733101
  45. Berggren PO, Yang SN, Murakami M, Efanov AM, Uhles S, Kohler M, Moede T, Fernstrom A, Appelskog IB, Aspinwall CA, Zaitsev SV, Larsson O, de Vargas LM, Fecher-Trost C, Weissgerber P, Ludwig A, Leibiger B, Juntti-Berggren L, Barker CJ, Gromada J, Freichel M, Leibiger IB, Flockerzi V. Removal of Ca2+ channel beta3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis. Cell. 2004; 119: 273-84. https://doi.org/10.1016/j.cell.2004.09.033
  46. Dyachok O, Idevall-Hagren O, Sagetorp J, Tian G, Wuttke A, Arrieumerlou C, Akusjarvi G, Gylfe E, Tengholm A. Glucose-induced cyclic AMP oscillations regulate pulsatile insulin secretion. Cell Metab. 2008; 8: 26-37. https://doi.org/10.1016/j.cmet.2008.06.003
  47. Gray PT. Oscillations of free cytosolic calcium evoked by cholinergic and catecholaminergic agonists in rat parotid acinar cells. J Physiol. 1988; 406: 35-53. https://doi.org/10.1113/jphysiol.1988.sp017367
  48. Futatsugi A, Nakamura T, Yamada MK, Ebisui E, Nakamura K, Uchida K, Kitaguchi T, Takahashi-Iwanaga H, Noda T, Aruga J, Mikoshiba K. IP3 receptor types 2 and 3 mediate exocrine secretion underlying energy metabolism. Science. 2005; 309: 2232-4. https://doi.org/10.1126/science.1114110