Perturbation of chemical coupling by an endothelial Cx40 mutant attenuates endothelium-dependent vasodilation by KCa channels and elevates blood pressure in mice

Pflugers Archiv European Journal of Physiology

Volumn 467, Issue 9, 2015, Pages 1997-2009

  Chaston, Daniel J ^a   Haddock, Rebecca E ^a   Howitt, Lauren ^a   Morton, Susan K ^a   Brown, Russell D ^b   Matthaei, Klaus I ^a   Hill, Caryl E ^a,c  

^a Australian National University   (Australia)

^b MONASH UNIVERSITY   (Australia)

^c AUSTRALIAN NATIONAL UNIVERSITY   (Australia)

Author keywords

Ascending vasodilation; Blood pressure; Connexin40; Endothelium; Locomotor activity; Potassium Channels

Indexed keywords

ACETYLCHOLINE; CONNEXIN 40; INTERMEDIATE CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNEL; N(G) NITROARGININE METHYL ESTER; PHENYLEPHRINE; RENIN; SMALL CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNEL; CALCIUM ACTIVATED POTASSIUM CHANNEL; GAP JUNCTION PROTEIN;

ANIMAL EXPERIMENT; ARTERIOLE; ARTICLE; BIOAVAILABILITY; BLOOD PRESSURE; CARDIOVASCULAR STRESS; CONTROLLED STUDY; CREMASTER MUSCLE; ENDOTHELIUM DEPENDENT VASODILATION; HEART RATE; IN VIVO STUDY; LOCOMOTION; MALE; MESENTERIC ARTERY; MOUSE; NONHUMAN; PLASMA RENIN ACTIVITY; POTASSIUM CONDUCTANCE; PRESSOR RESPONSE; PRIORITY JOURNAL; PULSE PRESSURE; STRESS; TELEMETRY; VASODILATATION; WILD TYPE; ANIMAL; C57BL MOUSE; GENETICS; HYPERTENSION; MEMBRANE POTENTIAL; METABOLISM; PATCH CLAMP TECHNIQUE; PATHOPHYSIOLOGY; PHYSIOLOGY; TRANSGENIC MOUSE; VASCULAR ENDOTHELIUM;

ANIMALS; BLOOD PRESSURE; CONNEXINS; ENDOTHELIUM, VASCULAR; HYPERTENSION; MALE; MEMBRANE POTENTIALS; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; PATCH-CLAMP TECHNIQUES; POTASSIUM CHANNELS, CALCIUM-ACTIVATED; VASODILATION;

EID: 84943449742     PISSN: 00316768     EISSN: 14322013     Source Type: Journal    
DOI: 10.1007/s00424-014-1640-x     Document Type: Article

References (43)

1. Bai D (2014) Atrial fibrillation-linked GJA5/connexin40 mutants impaired gap junctions via different mechanisms. FEBS Lett 588: 1238–1243
2. Boettcher M, de Wit C (2011) Distinct endothelium-derived hyperpolarizing factors emerge in vitro and in vivo and are mediated in part via connexin 40-dependent myoendothelial coupling. Hypertension 57:802–808
3. Brähler S, Kaistha A, Schmidt VJ, Wölfle SE, Busch C, Kaistha BP, Kacik M, Hasenau A-L, Grgic I, Si H, Bond CT, Adelman JP, Wulff H, de Wit C, Hoyer J, Köhler R (2009) Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension. Circulation 119: 2323–2332
4. Brown RD, Thoren P, Steege A, Mrowka R, Sallstrom J, Skott O, Fredholm BB, Persson AE (2006) Influence of the adenosine A1 receptor on blood pressure regulation and renin release. AmJ Physiol Regul Integr Comp Physiol 290:R1324–1329
5. Chaston DJ, Baillie BK, Grayson TH, Courjaret RJ, Heisler JM, Lau KA, Machaca K, Nicholson BJ, Ashton A, Matthaei KI, Hill CE (2013) Polymorphismin endothelial connexin40 enhances sensitivity to intraluminal pressure and increases arterial stiffness. Arterioscler, Thromb, Vasc Biol 33:962–970
6. Chaytor AT, Evans WH, Griffith TM (1997) Peptides homologous to extracellular loop motifs of connexin 43 reversibly abolish rhythmic contractile activity in rabbit arteries. J Physiol 503(Pt 1):99–110
7. Coleman HA, Tare M, Parkington HC (2001) K+ currents underlying the action of endothelium-derived hyperpolarizing factor in guineapig, rat and human blood vessels. J Physiol 531:359–373
8. Cronin CA, Gluba W, Scrable H (2001) The lac operator-repressor system is functional in the mouse. Genes Dev 15:1506–1517
9. deWit C, Roos F, Bolz SS, Kirchhoff S, Kruger O, Willecke K, Pohl U (2000) Impaired conduction of vasodilation along arterioles in connexin40-deficient mice. Circ Res 86:649–655
10. Edwards G, Gardener MJ, Feletou M, Brady G, Vanhoutte PM, Weston AH (1999) Further investigation of endothelium-derived hyperpolarizing factor (EDHF) in rat hepatic artery: studies using 1-EBIO and ouabain. Br J Pharmacol 128:1064–1070
11. Eichler I, Wibawa J, Grgic I, Knorr A, Brakemeier S, Pries AR, Hoyer J, Kohler R (2003) Selective blockade of endothelial Ca2+- activated small- and intermediate-conductance K+-channels suppresses EDHF-mediated vasodilation. Br J Pharmacol 138:594–601
12. Emerson GG, Segal SS (2000) Endothelial cell pathway for conduction of hyperpolarization and vasodilation along hamster feed artery. Circ Res 86:94–100
13. Emerson GG, Segal SS (2001) Electrical activation of endothelium evokes vasodilation and hyperpolarization along hamster feed arteries. Am J Physiol Heart Circ Physiol 280:H160–167
14. Firouzi M, Kok B, Spiering W, Busjahn A, Bezzina C, Ruijter J, Koeleman B, Schipper M, Groenewegen W, Jongsma H, de Leeuw P (2006) Polymorphisms in human connexin40 gene promoter are associated with increased risk of hypertension in men. J Hypertens 24:325–330
15. Garami A, Pakai E, Oliveira DL, Steiner AA, Wanner SP, Almeida MC, Lesnikov VA, Gavva NR, Romanovsky AA (2011) Thermoregulatory phenotype of the Trpv1 knockout mouse: thermoeffector dysbalance with hyperkinesis. J Neurosci 31:1721–1733
16. Gollob MH, Jones DL, Krahn AD, Danis L, Gong XQ, Shao Q, Liu X, Veinot JP, Tang AS, Stewart AF, Tesson F, Klein GJ, Yee R, Skanes AC, Guiraudon GM, Ebihara L, Bai D (2006) Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation. N Engl J Med 354:2677–2688
17. Griffith TM, Chaytor AT, Edwards DH (2004) The obligatory link: role of gap junctional communication in endothelium-dependent smooth muscle hyperpolarization. Pharmacol Res 49:551–564
18. Haddock RE, Grayson TH, Brackenbury TD, Meaney KR, Neylon CB, Sandow SL, Hill CE (2006) Endothelial coordination of cerebral vasomotion via myoendothelial gap junctions containing connexins 37 and 40. Am J Physiol- Heart Circ Physiol 291:H2047–H2056
19. Heximer SP, Knutsen RH, Sun X, Kaltenbronn KM, Rhee MH, Peng N, Oliveira-dos-Santos A, Penninger JM, Muslin AJ, Steinberg TH, Wyss JM, Mecham RP, Blumer KJ (2003) Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice. J Clin Invest 111:445–452
20. Howitt L, Chaston DJ, Sandow SL, Matthaei KI, Edwards FR, Hill CE (2013) Spreading vasodilatation in the murine microcirculation: attenuation by oxidative stress-induced change in electromechanical coupling. J Physiol 591:2157–2173
21. Howitt L, Kuo IY, Ellis A, Chaston DJ, Shin HS, Hansen PB, Hill CE (2013) Chronic deficit in nitric oxide elicits oxidative stress and augments T-type calcium-channel contribution to vascular tone of rodent arteries and arterioles. Cardiovasc Res 98:449–457
22. Isakson BE, Best AK, Duling BR (2008) Incidence of protein on actin bridges between endothelium and smooth muscle in arterioles demonstrates heterogeneous connexin expression and phosphorylation. Am J Physiol Heart Circ Physiol 294:H2898–2904
23. Jobs A, Schmidt K, Schmidt VJ, Lubkemeier I, van Veen TAB, Kurtz A, Willecke K, de Wit C (2012) Defective Cx40 maintains Cx37 expression but intact Cx40 is crucial for conducted dilations irrespective of hypertension. Hypertension 60:1422–1429
24. Johnston CI, Mendelsohn F, Casley D (1971) Evaluation of renin and angiotensin assays and their clinical application. Med J Aust 1:126–128
25. Kansui Y, Garland CJ, Dora KA (2008) Enhanced spontaneous Ca2+ events in endothelial cells reflect signalling through myoendothelial gap junctions in pressurized mesenteric arteries. Cell Calcium 44: 135–146
26. Kopkan L, Hess A, Huskova Z, Cervenka L, Navar LG, Majid DS (2010)High-salt intake enhances superoxide activity in eNOS knockout mice leading to the development of salt sensitivity. Am J Physiol Renal Physiol 299:F656–663
27. Lamboley M, Pittet P, Koenigsberger M, Sauser R, Beny JL, Meister JJ (2005) Evidence for signaling via gap junctions from smooth muscle to endothelial cells in rat mesenteric arteries: possible implication of a second messenger. Cell Calcium 37:311–320
28. Makita N, Seki A, Sumitomo N, Chkourko H, Fukuhara S, Watanabe H, Shimizu W, Bezzina CR, Hasdemir C, Mugishima H, Makiyama T, Baruteau A, Baron E, Horie M, Hagiwara N, Wilde AA, Probst V, Le Marec H, Roden DM, Mochizuki N, Schott JJ, Delmar M (2012) A connexin40 mutation associated with a malignant variant of progressive familial heart block type I. Circ Arrhythm Electrophysiol 5: 163–172
29. Mather S, Dora KA, Sandow SL, Winter P, Garland CJ (2005) Rapid endothelial cell-selective loading of connexin 40 antibody blocks endothelium-derived hyperpolarizing factor dilation in rat small mesenteric arteries. Circ Res 97:399–407
30. Morton SK, Chaston DJ, Baillie BK, Hill CE, Matthaei KI (2014) Regulation of endothelial-specific transgene expression by the LacI repressor protein in vivo. PLoS One 9:e95980
31. Neild TO (1989) Measurement of arteriole diameter changes by analysis of television images. Blood Vessels 26:48–52
32. Nobrega AC, O'Leary D, Silva BM, Marongiu E, Piepoli MF, Crisafulli A (2014) Neural regulation of cardiovascular response to exercise: role of central command and peripheral afferents. Biomed Res Int 478965:9
33. Ryan A, Scrable H (2004) Visualization of the dynamics of gene expression in the living mouse. Mol Imaging 3:33–42
34. Sandow SL, Neylon CB, Chen MX, Garland CJ (2006) Spatial separation of endothelial small- and intermediate-conductance calcium- activated potassium channels (K(Ca)) and connexins: possible relationship to vasodilator function? J Anat 209:689–698
35. Sankaranarayanan A, Raman G, Busch C, Schultz T, Zimin PI, Hoyer J, Kohler R, Wulff H (2009) Naphtho[1,2-d]thiazol-2-ylamine (SKA- 31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure. Mol Pharmacol 75:281–295
36. Si H, Heyken WT, Wolfle SE, Tysiac M, Schubert R, Grgic I, Vilianovich L, Giebing G, Maier T, Gross V, Bader M, de Wit C, Hoyer J, Kohler R (2006) Impaired endothelium-derived hyperpolarizing factor-mediated dilations and increased blood pressure in mice deficient of the intermediate-conductance Ca2+-activated K+ channel. Circ Res 99:537–544
37. Tran CH, Taylor MS, Plane F, Nagaraja S, Tsoukias NM, Solodushko V, Vigmond EJ, Furstenhaupt T, Brigdan M, Welsh DG (2012) Endothelial Ca2+ wavelets and the induction of myoendothelial feedback. Am J Physiol Cell Physiol 302:C1226–1242
38. VanderBrink BA, Sellitto C, Saba S, Link MS, Zhu W, Homoud MK, Estes NA III, Paul DL, Wang PJ (2000) Connexin40-deficient mice exhibit atrioventricular nodal and infra-Hisian conduction abnormalities. J Cardiovasc Electrophysiol 11:1270–1276
39. Wagner C, Jobs A, Schweda F, Kurtz L, Kurt B, Lopez ML, Gomez RA, van Veen TA, de Wit C, Kurtz A (2010) Selective deletion of Connexin 40 in renin-producing cells impairs renal baroreceptor function and is associated with arterial hypertension. Kidney Int 78: 762–768
40. Warner A, Clements DK, Parikh S, Evans WH, DeHaan RL (1995) Specific motifs in the external loops of connexin proteins can determine gap junction formation between chick heartmyocytes. J Physiol 488(Pt 3):721–728
41. Wölfle SE, Chaston DJ, Goto K, Sandow SL, Edwards FR, Hill CE (2011) Non-linear relationship between hyperpolarisation and relaxation enables long distance propagation of vasodilatation. J Physiol 589:2607–2623
42. Yang Y-Q, Liu X, Zhang X-L, Wang X-H, Tan H-W, Shi H-F, Jiang W-F, Fang W-Y (2010) Novel connexin40 missense mutations in patients with familial atrial fibrillation. Europace 12:1421–1427
43. Yeh H-I, Rothery S, Dupont E, Coppen SR, Severs NJ (1998) Individual gap junction plaques containmultiple connexins in arterial endothelium. Circ Res 83:1248–1263