Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Jul 9

PMID 35806312

Authors

Pia C Burboa

Mariela Puebla

Pablo S Gaete

Walter N Duran

Mauricio A Lillo

Affiliations

Soon will be listed here.

Abstract

Microcirculation homeostasis depends on several channels permeable to ions and/or small molecules that facilitate the regulation of the vasomotor tone, hyperpermeability, the blood-brain barrier, and the neurovascular coupling function. Connexin (Cxs) and Pannexin (Panxs) large-pore channel proteins are implicated in several aspects of vascular physiology. The permeation of ions (i.e., Ca) and key metabolites (ATP, prostaglandins, D-serine, etc.) through Cxs (i.e., gap junction channels or hemichannels) and Panxs proteins plays a vital role in intercellular communication and maintaining vascular homeostasis. Therefore, dysregulation or genetic pathologies associated with these channels promote deleterious tissue consequences. This review provides an overview of current knowledge concerning the physiological role of these large-pore molecule channels in microcirculation (arterioles, capillaries, venules) and in the neurovascular coupling function.

Citing Articles

Endothelial TRPV4/Cx43 Signaling Complex Regulates Vasomotor Tone in Resistance Arteries.

Burboa P, Gaete P, Shu P, Araujo P, Beuve A, Duran W bioRxiv. 2024; .

PMID: 39091840 PMC: 11291137. DOI: 10.1101/2024.07.25.604930.

Impact of Matrix Gel Variations on Primary Culture of Microvascular Endothelial Cell Function.

Burboa P, Correa-Velloso J, Arriagada C, Thomas A, Duran W, Lillo M Microcirculation. 2024; 31(5):e12859.

PMID: 38818977 PMC: 11227414. DOI: 10.1111/micc.12859.

The role of enhanced expression of Cx43 in patients with ulcerative colitis.

Liu W, Feng Y, Li T, Shi T, Hui W, Liu H Open Med (Wars). 2024; 19(1):20230885.

PMID: 38770177 PMC: 11103162. DOI: 10.1515/med-2023-0885.

Pannexins in the musculoskeletal system: new targets for development and disease progression.

Luo Y, Zheng S, Xiao W, Zhang H, Li Y Bone Res. 2024; 12(1):26.

PMID: 38705887 PMC: 11070431. DOI: 10.1038/s41413-024-00334-8.

Pannexin1: insight into inflammatory conditions and its potential involvement in multiple organ dysfunction syndrome.

Chen X, Yuan S, Mi L, Long Y, He H Front Immunol. 2023; 14:1217366.

PMID: 37711629 PMC: 10498923. DOI: 10.3389/fimmu.2023.1217366.

References

Moller S, Brings Jacobsen J, Holstein-Rathlou N, Sorensen C . Lack of Connexins 40 and 45 Reduces Local and Conducted Vasoconstrictor Responses in the Murine Afferent Arterioles. Front Physiol. 2020; 11:961. PMC: 7431600. DOI: 10.3389/fphys.2020.00961. View

Lourenco C, Laranjinha J . Nitric Oxide Pathways in Neurovascular Coupling Under Normal and Stress Conditions in the Brain: Strategies to Rescue Aberrant Coupling and Improve Cerebral Blood Flow. Front Physiol. 2021; 12:729201. PMC: 8569710. DOI: 10.3389/fphys.2021.729201. View

Myers J, Haddad B, ONeill S, Chorev D, Yoshioka C, Robinson C . Structure of native lens connexin 46/50 intercellular channels by cryo-EM. Nature. 2018; 564(7736):372-377. PMC: 6309215. DOI: 10.1038/s41586-018-0786-7. View

Yamaguchi D, Ma D . Mechanism of pH regulation of connexin 43 expression in MC3T3-E1 cells. Biochem Biophys Res Commun. 2003; 304(4):736-9. DOI: 10.1016/s0006-291x(03)00633-8. View

Good M, Chiu Y, Poon I, Medina C, Butcher J, Mendu S . Pannexin 1 Channels as an Unexpected New Target of the Anti-Hypertensive Drug Spironolactone. Circ Res. 2017; 122(4):606-615. PMC: 5815904. DOI: 10.1161/CIRCRESAHA.117.312380. View

Saez J, Contreras-Duarte S, Gomez G, Labra V, Santibanez C, Gajardo-Gomez R . Connexin 43 Hemichannel Activity Promoted by Pro-Inflammatory Cytokines and High Glucose Alters Endothelial Cell Function. Front Immunol. 2018; 9:1899. PMC: 6104120. DOI: 10.3389/fimmu.2018.01899. View

van Kempen M, Jongsma H . Distribution of connexin37, connexin40 and connexin43 in the aorta and coronary artery of several mammals. Histochem Cell Biol. 2000; 112(6):479-86. DOI: 10.1007/s004180050432. View

Brisset A, Isakson B, Kwak B . Connexins in vascular physiology and pathology. Antioxid Redox Signal. 2008; 11(2):267-82. PMC: 2819334. DOI: 10.1089/ars.2008.2115. View

Vargas A, Cisterna B, Saavedra-Leiva F, Urrutia C, Cea L, Vielma A . On Biophysical Properties and Sensitivity to Gap Junction Blockers of Connexin 39 Hemichannels Expressed in HeLa Cells. Front Physiol. 2017; 8:38. PMC: 5298994. DOI: 10.3389/fphys.2017.00038. View

10.

Lai Y, Huang Y . Mechanisms of Mechanical Force Induced Pulmonary Vascular Endothelial Hyperpermeability. Front Physiol. 2021; 12:714064. PMC: 8521004. DOI: 10.3389/fphys.2021.714064. View

11.

Retamal M, Schalper K, Shoji K, Bennett M, Saez J . Opening of connexin 43 hemichannels is increased by lowering intracellular redox potential. Proc Natl Acad Sci U S A. 2007; 104(20):8322-7. PMC: 1895948. DOI: 10.1073/pnas.0702456104. View

12.

ODonnell 3rd J, Birukova A, Beyer E, Birukov K . Gap junction protein connexin43 exacerbates lung vascular permeability. PLoS One. 2014; 9(6):e100931. PMC: 4072707. DOI: 10.1371/journal.pone.0100931. View

13.

Harris A, Contreras J . Motifs in the permeation pathway of connexin channels mediate voltage and Ca (2+) sensing. Front Physiol. 2014; 5:113. PMC: 3978323. DOI: 10.3389/fphys.2014.00113. View

14.

Hatakeyama T, Pappas P, Hobson 2nd R, Boric M, Sessa W, Duran W . Endothelial nitric oxide synthase regulates microvascular hyperpermeability in vivo. J Physiol. 2006; 574(Pt 1):275-81. PMC: 1817804. DOI: 10.1113/jphysiol.2006.108175. View

15.

Ahmadpour N, Kantroo M, Stobart J . Extracellular Calcium Influx Pathways in Astrocyte Calcium Microdomain Physiology. Biomolecules. 2021; 11(10). PMC: 8533159. DOI: 10.3390/biom11101467. View

16.

Kusano Y, Echeverry G, Miekisiak G, Kulik T, Aronhime S, Chen J . Role of adenosine A2 receptors in regulation of cerebral blood flow during induced hypotension. J Cereb Blood Flow Metab. 2009; 30(4):808-15. PMC: 2949168. DOI: 10.1038/jcbfm.2009.244. View

17.

Edwards G, Dora K, Gardener M, Garland C, Weston A . K+ is an endothelium-derived hyperpolarizing factor in rat arteries. Nature. 1998; 396(6708):269-72. DOI: 10.1038/24388. View

18.

Contreras J, Saez J, Bukauskas F, Bennett M . Gating and regulation of connexin 43 (Cx43) hemichannels. Proc Natl Acad Sci U S A. 2003; 100(20):11388-93. PMC: 208767. DOI: 10.1073/pnas.1434298100. View

19.

Johnstone S, Kroncke B, Straub A, Best A, Dunn C, Mitchell L . MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth muscle cell proliferation. Circ Res. 2012; 111(2):201-11. PMC: 3405546. DOI: 10.1161/CIRCRESAHA.112.272302. View

20.

Kwak B, Mulhaupt F, Veillard N, Gros D, Mach F . Altered pattern of vascular connexin expression in atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 2002; 22(2):225-30. DOI: 10.1161/hq0102.104125. View