Abstract
Microcirculation is the generic name for the finest level of the circulatory system and consists of arteriolar and venular networks located upstream and downstream of capillaries, respectively. Anatomically arterioles are surrounded by a monolayer of spindle-shaped smooth muscle cells (myocytes), while terminal branches of precapillary arterioles, capillaries and all sections of postcapillary venules are surrounded by a monolayer of morphologically different perivascular cells (pericytes). Pericytes are essential components of the microvascular vessel wall. Wrapped around endothelial cells, they occupy a strategic position at the interface between the circulating blood and the interstitial space. There are physiological differences in the responses of pericytes and myocytes to vasoactive molecules, which suggest that these two types of vascular cells could have different functional roles in the regulation of local blood flow within the same microvascular bed. Also, pericytes may play different roles in different microcirculatory beds to meet the characteristics of individual organs. Contractile activity of pericytes and myocytes is controlled by changes of cytosolic free Ca2+concentration. In this chapter, we attempt to summarize the results in the field of Ca2+ signalling in pericytes especially in light of their contractile roles in different tissues and organs. We investigate the literature and describe our results regarding sources of Ca2+, relative importance and mechanisms of Ca2+ release and Ca2+ entry in control of the spatio-temporal characteristics of the Ca2+ signals in pericytes, where possible Ca2+ signalling and contractile responses in pericytes are compared to those of myocytes.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ammendola A, Geiselhöringer A, Hofmann F, Schlossmann J (2001) Molecular determinants of the interaction between the inositol 1,4,5- trisphosphate receptor-associated cGMP kinase substrate (IRAG) and cGMP kinase I beta. J Biol Chem 276:24153–24159
Attwell D, Mishra A, Hall CN, O’Farrell FM, Dalkara T (2016) What is a pericyte? JCBM 36:451–455
Beach JM, McGahren ED, Duling BR (1998) Capillaries and arterioles are electrically coupled in hamster cheek pouch. Am J Physiol Heart Circ Physiol 275:H1489–H1496
Berg BR, Cohen KD, Sarelius IH (1997) Direct coupling between blood flow and metabolism at the capillary level in striated muscle. Am J Physiol Heart Circ Physiol 272:H2693–H2700
Bertlich M, Ihler F, Weiss BG, Saskia Freytag S, Strupp M, Jakob M, Canis M (2017) Role of capillary pericytes and precapillary arterioles in the vascular mechanism of betahistine in a guinea pig inner ear model. Life Sci 187:17–21
Boado RJ, Pardridge WM (1994) Differential expression of alpha-actin mRNA and immunoreactive protein in brain microvascular pericytes and smooth muscle cells. J Neurosci Res 39:430–435
Borisova L, Wray S, Eisner DA, Burdyga T (2009) How structure, Ca signals, and cellular communications underlie function in precapillary arterioles. Circ Res 105:803–810
Borysova L, Wray S, Eisner D, Burdyga T (2013) How calcium signals in myocytes and pericytes are integrated across in situ microvascular networks and control microvascular tone. Cell Calcium 54:163–174
Borysova L, Burdyga T (2015) Evidence that NO/cGMP/PKG signalling cascade mediates endothelium dependent inhibition of IP3R mediated Ca2+ oscillations in myocytes and pericytes of ureteric microvascular network in situ. Cell Calcium 58:535–540
Burdyga TV, Shmigol A, Eisner DA, Wray S (2003) A new technique for simultaneous and in situ measurements of Ca signals in arteriolar smooth muscle and endothelial cells. Cell Calcium 34:27–33
Chakravarthy U, Gardiner TA, Archer DB, Trimble ER (1992) The effect of endothelin 1 on the retinal microvascular pericyte. Microvasc Res 43:241–254
Condren AB, Kumar A, Mettu P, Liang KJ, Zhao L, Tsai J, Fariss RN, Wong WT (2013) Perivascular mural cells of the mouse choroid demonstrate morphological diversity that is correlated to vasoregulatory function. PLoS One 8:1–13
Carvajal JA, Germain AM, Huidobro-Toro JP, Weiner CP (2000) Molecular mechanism of cGMP-mediated smooth muscle relaxation. J Cell Physiol 184:409–420
DeNofrio D, Hoock TC, Herman IM (1989) Functional sorting of actin isoforms in microvascular pericytes. J Cell Biol 109:191–202
Dehouck MP, Vigne P, Torpier G, Breittmayer JP, Cecchelli R, Frelin C (1997) Endothelin-1 as a mediator of endothelial cell-pericyte interactions in bovine brain capillaries. J Cereb Blood Flow Metab 17:464–469
Diaz-Flores L, Gutierrez R, Madrid JF, Varela H, Valladares F, Acosta E, Martin-Vasallo P, Diaz-Flores L Jr (2009) Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. Histol Histopathol 24:909–969
Droogmans G, Raeymaekers L, Casteels R (1977) Electro- and pharmacomechanical coupling in the smooth muscle cells of the rabbit ear artery. J Gen Physiol 70:129–148
Feil R, Gappa N, Rutz M, Schlossmann J, Rose CR, Konnerth A, Brummer S, Kuhbandner S, Hofmann F (2002) Functional reconstitution of vascular smooth muscle cells with cGMP-dependent protein kinase I isoforms. Circ Res 90:1080–1086
Fujiwara T, Tenkova TI, Kondo M (1999) Wall cytoarchitecture of the rat ciliary process microvasculature revealed with scanning electron microscopy. Anat Rec 254:261–268
Fujiwara S, Ito Y, Itoh T, Kuriyama H, Suzuki H (1982) Diltiazem-induced vasodilatation of smooth muscle cells of the canine basilar artery. Br J Pharmacol 75:455–467
Fujiwara S, Kuriyama H (1983) Effects of agents that modulate potassium permeability on smooth muscle cells of the guinea-pig basilar artery. Br J Pharmacol 79:23–35
Hashitani H, Takano H, Fujita K, Mitsui R, Suzuki H (2011) Functional properties of suburothelial microvessels in the rat bladder. J Urol 185:2382–2391
Hashitani H, Mitsui R, Shimizu Y, Higashi R, Nakamura K (2012) Functional and morphological properties of pericytes in suburothelial venules of the mouse bladder. Br J Pharmacol 167:1723–1736
Hashitani H, Mitsui R, Masaki S, Van Helden DF (2015) Pacemaker role of pericytes in generating synchronized spontaneous Ca2+ transients in the myenteric microvasculature of the guinea-pig gastric antrum. Cell Calcium 58:442–456
Hashitani H, Lang R (2016) Spontaneous activity in the microvasculature of visceral organs: role of pericytes and voltage-dependent Ca2+ channels. J Physiol 594:555–565
Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, O’Farrell FM, Buchan AM, Lauritzen M, Attwell D (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508:55–60
Hartmann DA, Underly RG, Grant RI, Lindner V, Shih AY (2015) Pericyte structure and distribution in the cerebral cortex revealed by high resolution imaging of transgenic mice. Neurophotonics 2:041401–041413
Helbig H, Kornacker S, Berweck S, Stahl F, Lepple-Wienhues A, Wiederholt M (1992) Membrane potentials in retinal capillary pericytes: excitability and effect of vasoactive substances. Invest Ophthalmol Vis Sci 33:2105–2112
Higuchi K, Hashizume H, Aizawa Y, Ushiki T (2000) Scanning electron microscopic studies of the vascular smooth muscle cells and pericytes in the rat heart. Arch Histol Cytol 63:115–126
Hill RA, Tong L, Yuan P, Murikinati S, Shobhana Gupta S, Jaime Grutzendler J (2015) Regional blood flow in the normal and ischemic brain is controlled by arteriolar smooth muscle cell contractility and not by capillary pericytes. Neuron 87:95–110
Iijima T, Zhang JQ (2002) Three-dimensional wall structure and the innervations of dental pulp blood vessels. Microsc Res Tech 56:32–41
Iino M, Kasai H, Yamazawa T (1994) Visualization of neural control of intracellular Ca 2+ concentration in single vascular smooth muscle cells in situ. EMBO J 13:5026–5031
Ishizaki E, Fukumoto M, Puro DG (2009) Functional K (ATP) channels in the rat retinal microvasculature: topographical distribution, redox regulation, spermine modulation and diabetic alteration. J Physiol 587:2233–2253
Itoh T, Kuriyama H, Suzuki H (1981) Excitation-contraction coupling in smooth muscle cells of the guinea-pig mesenteric artery. J Physiol 321:513–535
Ivanova E, Kovacs-Oller T, Sagdullaev BT (2017) Vascular pericyte impairment and connexin 43 gap junction deficit contribute to vasomotor decline in diabetic retinopathy. J Neurosci 37:7580–7594
Jima T, Zhang JQ, Goto T, Kondo T, Tanaka T (1991) A scanning electron microscopic study of the contraction of vascular wall cells in dog dental. J Dent Res 70:1456–1461
Joyce NC, Haire MF, Palade GE (1985) Contractile proteins in pericytes. Immunoperoxidase localization of tropomyosin. J Cell Blot 100:1379–1386
Joyce NC, DeCamilli P, Boyles J (1984) Pericytes, like vascular smooth muscle cells, are immunocytochemically positive for cyclic GMP-dependent protein kinase. Microvasc Ret 28:206–219
Kanmura Y, Itoh T, Suzuki H, Ito Y, Kuriyama H (1983) Effects of nifedipine on smooth muscle cells of the rabbit mesenteric artery. J Pharmacol Exp Ther 226:238–248
Kamouchi M, Kitazono T, Ago T, Wakisaka M, Ooboshi H, Ibayashi S, Iida M (2004) Calcium influx pathways in rat CNS pericytes. Brain Res Mol Brain Res 126:114–120
Kamouchi M, Kitazono T, Ago T, Wakisaka M, Kuroda J, Nakamura K, Hagiwara N, Ooboshi H, Ibayashi S, Iida M (2007) Hydrogen peroxide-induced Ca 2+ responses in CNS pericytes. Neurosci Lett 416:12–16
Kawamura H, Kobayashi M, Li Q, Yamanishi S, Katsumura K, Minami M, Wu DM, Puro DG (2004) Effects of angiotensin II on the pericyte containing microvasculature of the rat retina. J Physiol 561:671–683
Klitzman B, Damon DN, Gorczynski RJ, Duling BR (1982) Augmented tissue oxygen supply during striated muscle contraction in the hamster. Relative contributions of capillary recruitment, functional dilation, and reduced tissue PO2. Circ Res 51:711–721
Lee-Kwon W, Wade JB, Zhang Z, Pallone TL, Weinman EJ (2005) Expression of TRPC4 channel protein that interacts with NHERF-2 in rat descending vasa recta. Am J Physiol Cell Physiol 288:C942–C949
Lindbom L, Arfors KE (1984) Non-homogeneous blood flow distribution in the rabbit tenuissimus muscle. Differential control of total blood flow and capillary perfusion. Acta Physiol Scand 122:225–233
Liu YH, Zhang ZP, Wang Y, Song J, Ma KT, Si JQ, Li L (2018) Electrophysiological properties of strial pericytes and the effect of aspirin on pericyte K+ channels. Mol Med Rep 17:2861–2868
Majno G, Shea SM, Leventhal M (1969) Endothelial contraction induced by histamine – type mediators. J Cell Biol 42:647–672
Marshall JM, Lloyd J, Mian R (1993) The influence of vasopressin on the arterioles and venules of skeletal muscle of the rat during systemic hypoxia. J Physiol 470:473–484
Matsushita K, Fukumoto M, Kobayashi T, Kobayashi M, Ishizaki E, Minami M, Katsumura K, Liao SD, Wu DM, Zhang T, Puro DG (2010) Diabetes-induced inhibition of voltage-dependent calcium channels in the retinal microvasculature: role of spermine. Invest Ophthalmol Vis Sci 51:5979–5990
Matsushita K, Puro DG (2006) Topographical heterogeneity of KIR currents in pericyte-containing microvessels of the rat retina: effect of diabetes. J Physiol 573:483–495
McGinty A, Scholfield CN, Liu WH, Anderson P, Hoey DE, Trimble ER (1999) Effect of glucose on endothelin-1-induced calcium transients in cultured bovine retinal pericytes. J Biol Chem 274:25250–25253
Mitsui R, Miyamoto S, Takano H, Hashitani H (2013) Properties of submucosal venules in the rat distal colon. Br J Pharmacol 170:968–977
Mitsui R, Hashitani H (2015) Functional properties of submucosal venules in the rat stomach. Pflugers Arch – Eur J Physiol 467:1327–1342
Mitsui R, Hashitani H (2016) Mechanisms underlying spontaneous constrictions of postcapillary venules in the rat stomach. Pflugers Arch – Eur J Physiol 468:279–291
Mitsui R, Hashitani H (2017) Properties of synchronous spontaneous Ca2+ transients in the mural cells of rat rectal arterioles. Pflugers Arch – Eur J Physiol 469:1189–1202
Mitsui R, Hashitani H (2013) Immunohistochemical characteristics of suburothelial microvasculature in the mouse bladder. Histochem Cell Biol 140:189–200
Morgan KG (1983) Comparison of membrane electrical activity of cat gastric submucosal arterioles and venules. J Physiol 345:135–147
Mogensen C, Bergner B, Wallner S, Ritter A, D’Avis S, Ninichuk V, Kameritsch P, Gloe T, Nagel W, Pohl U (2011) Isolation and functional characterization of pericytes derived from hamster skeletal muscle. Acta Physiol 201:413–426
Murphy DD, Wagner RC (1994) Differential contractile response of cultured microvascular pericytes to vasoactive agents. Microcirculation 1:121–128
Nakai K, Imai H, Kamei I, Itakura T, Komari N, Kimura H, Nagai T, Maeda T (1981) Microangioarchitecture of rat parietal cortex with special reference to vascular ‘sphincters’. Scanning electron microscopic and dark field microscopic study. Stroke 12:653–659
Nees S, Juchem G, Eberhorn N, Thallmair M, Förch S, Knott M, Senftl A, Fischlein T, Reichart B, Weiss DR (2012) Wall structures of myocardial precapillary arterioles and postcapillary venules reexamined and reconstructed in vitro for studies on barrier functions. Am J Physiol Heart Circ Physiol 302:H51–H68
Nehls V, Drenckhahn D (1991) Heterogeneity of microvascular pericytes for smooth muscle type alpha-actin. J Cell Biol 113:147–154
O’Farrell FM, Mastitskaya S, Hammond-Haley M, Freitas F, Wen RuiWah WR, Attwell D (2017) Capillary pericytes mediate coronary no-reflow after myocardial ischaemia. ELife 6. pii:e29280. https://doi.org/10.7554/eLive.29280
O’Farrell FM, Attwell D (2014) A role for pericytes in coronary noreflow. Nat Rev Cardiol 11:427–432
Oku H, Kodama T, Sakagami Wu DM, Miniami M, Kawamura H, Puro DG (2006) Electrotonic transmission within pericyte-containing retinal microvessels. Microcirculation 13:353–363
Pallone TL, Huang JM (2002) Control of descending vasa recta pericyte membrane potential by angiotensin II. Am J Phys 282:F1064–F1074
Pallone TL, Zhang Z, Rhinehart K (2003) Physiology of the renal medullary microcirculation. Am J Physiol Renal Physiol 284:F253–F266
Pannarale L, Onori P, Ripani M, Gaudio E (1996) Precapillary patterns and perivascular cells in the retinal microvasculature. A scanning electron microscopic study. J Anat 188:693–703
Perez JF, Sanderson MJ (2005) The contraction of smooth muscle cells of intrapulmonary arterioles is determined by the frequency of Ca 2+ oscillations induced by 5-HT and KCl. J Gen Physiol 125:555–567
Puro DG (2007) Physiology and pathobiology of the pericyte-containing retinal microvasculature: new developments. Microcirculation 14:1–10
Ramachandran E, Frank RN, Kennedy A (1993) Effects of endothelin on cultured bovine retinal microvascular pericytes. Invest Ophthalmol Vis Sci 34:586–595
Rhinehart K, Zhang Z, Pallone TL (2002) Ca2+ signaling and membrane potential in descending vasa recta pericytes and endothelia. Am J Phys 283:F852–F860
Sarelius IH (1986) Cell flow path influences transit time through striated muscle capillaries. Am J Phys 250:H899–H907
Sakagami K, Wu DM, Puro DG (1999) Physiology of rat retinal pericytes: modulation of ion channel activity by serum-derived molecules. J Physiol 521:637–650
Scholfield CN, Curtis TM (2000) Heterogeneity in cytosolic calcium regulation among different microvascular smooth muscle cells of the rat retina. Microvasc Res 59:233–242
Shepro D, Morel NM (1993) Pericyte physiology. FASEB J 7:1031–1038
Sims DE (1991) Recent advances in pericyte biology – implications for health and disease. Can J Cardiol 7:431–443
Silldorff EP, Yang S, Pallone TL (1995) Prostaglandin E2 abrogates endothelin-induced vasoconstriction in renal outer medullary descending vasa recta of the rat. J Clin Invest 95:2734–2740
Schlossmann J, Ammendola A, Ashman K, Zong XG, Huber A, Neubauer G, Wang GX, Allescher HD, Korth M, Wilm M, Hofmann F, Ruth P (2000) Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase I beta. Nature 404:197–201
Stark K, Eckart A, Haidari S, Tirniceriu A, Lorenz M, von Brühl ML, Gärtner F, Khandoga AG, Legate KR, Pless R, Hepper I, Lauber K, Walzog B, Massberg S (2013) Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and ‘instruct’ them with pattern-recognition and motility programs. Nat Immunol 14:41–51
Tumelty J, Hinds K, Bankhead P, McGeown NJ, Scholfield C, Curtis TM, McGeown JG (2011) Endothelin 1 stimulates Ca2+ sparks and oscillations in retinal arteriolar myocytes via IP 3 R and RyR-dependent Ca2+ release. Invest Ophthalmol Vis Sci 52:3874–3879
Vates GE, Takano T, Zlokovic B, Nedergaard M (2010) Pericyte constriction after stroke: the jury is still out. Nat Med 16:959 author reply, 960
Wu DM, Miniami M, Kawamura H, Puro DG (2006) Electrotonic transmission within pericyte-containing retinal microvessels. Microcirculation 13:353–363
Wu DM, Kawamura H, Sakagami K, Kobayashi M, Puro DG (2003) Cholinergic regulation of pericyte-containing retinal microvessels. Am J Physiol Heart Circ Physiol 284:H2083–H2090
Yamanishi S, Katsumura K, Kobayashi T, Puro DG (2006) Extracellular lactate as a dynamic vasoactive signal in the rat retinal microvasculature. Am J Phys 290:H925–H934
Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T (2009) Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med 15:1031–1037
Zhang Z, Cao C, Lee-Kwon W, Pallone TL (2005) Descending vasa recta pericytes express voltage operated Na + conductance in the rat. J Physiol 567:445–457
Zhang T, Wu DM, Xu GZ, Puro DG (2011) The electrotonic architecture of the retinal microvasculature: modulation by angiotensin II. J Physiol 589:2383–2399
Zhang Z, Rhinehart K, Pallone TL (2002) Membrane potential controls calcium entry into descending vasa recta pericytes. Am J Phys 283:R949–R957
Zhang Z, Payne K, Cao C, Pallone TL (2013) Mural propagation of descending vasa recta responses to mechanical stimulation. Am J Physiol Renal Physiol 305:F286–F294
Zhang HR (1994) Scanning electron microscopic study of corrosion casts on retinal and choroidalangio architecture in man and animals. Prog Retin Eye Res 13:243–270
Zhang Q, Cao C, Zhang Z, Wier WG, Edwards A, Pallone TL (2008) Membrane current oscillations in descending vasa recta pericytes. Am J Physiol Renal Physiol 294:F656–F666
Zimmerman KW (1923) Der feinere Bau der Blutcappillaren. Z Anat Entwicklungsgesch 68:29–109
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Burdyga, T., Borysova, L. (2018). Ca2+ Signalling in Pericytes. In: Birbrair, A. (eds) Pericyte Biology - Novel Concepts. Advances in Experimental Medicine and Biology, vol 1109. Springer, Cham. https://doi.org/10.1007/978-3-030-02601-1_8
Download citation
DOI: https://doi.org/10.1007/978-3-030-02601-1_8
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-02600-4
Online ISBN: 978-3-030-02601-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)