Pharmacologic targeting of endothelial Ca²⁺-activated K⁺ channels: A strategy to improve cardiovascular function

References

• Edwards G, Feletou M, Weston AH. Endothelium-derived hyperpolarising factors and associated pathways: a synopsis. Pflugers Archiv: European Journal of Physiology. 2010;459(6):863–79.
   PubMed Web of Science ®Google Scholar
• Hasenau AL, Nielsen G, Morisseau C, et al. Improvement of endothelium-dependent vasodilations by SKA-31 and SKA-20, activators of small- and intermediate-conductance Ca2+ -activated K+ -channels. Acta Physiologica. 2011;203(1):117–26.
   PubMed Web of Science ®Google Scholar
• Köhler R, Kaistha BP, Wulff H. Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease. Expert Opin Ther Targets. 2010;14(2):143–55.
   PubMed Web of Science ®Google Scholar
• Gueguinou M, Chantome A, Fromont G, et al. KCa and Ca2+ channels: the complex thought. Biochim et Biophys Acta. 2014;1843(10):2322–33.
   PubMed Web of Science ®Google Scholar
• Mishra RC, Wulff H, Cole WC, et al. A pharmacologic activator of endothelial KCa channels enhances coronary flow in the hearts of type 2 diabetic rats. J Mol Cell Cardiol. 2014;72:364–73.
   PubMed Web of Science ®Google Scholar
• Sheng JZ, Ella S, Davis MJ, et al. Openers of SKCa and IKCa channels enhance agonist-evoked endothelial nitric oxide synthesis and arteriolar vasodilation. FASEB J. 2009;23(4):1138–45.
   PubMed Web of Science ®Google Scholar
• Dong DL, Bai YL, Cai BZ. Calcium-Activated Potassium Channels: Potential Target for Cardiovascular Diseases. Adv Protein Chem Struct Biol. 2016;104:233–261.
   PubMed Web of Science ®Google Scholar
• Hansen LK. The role of T cell potassium channels, KV1.3 and KCa3.1, in the inflammatory cascade in ulcerative colitis. Dan Med J. 2014;61(11):B4946.
   PubMedGoogle Scholar
• Mauricio MD, Serna E, Cortina B, et al. Role of Ca2+-activated K+ channels on adrenergic responses of human saphenous vein. Am J Hypertens. 2007;20(1):78–82.
   PubMed Web of Science ®Google Scholar
• Verheugen JA, van Kleef RG, Oortgiesen M, et al. Characterization of Ca2+-activated K+ channels in excised patches of human T lymphocytes. Pflugers Archiv: European Journal of Physiology. 1994;426(6):465–71.
   PubMed Web of Science ®Google Scholar
• Gillham JC, Myers JE, Baker PN, et al. Regulation of endothelial-dependent relaxation in human systemic arteries by SKCa and IKCa channels. Reproductive Sciences. 2007;14(1):43–50.
   PubMed Web of Science ®Google Scholar
• Wulff H, Kolski-Andreaco A, Sankaranarayanan A, et al. Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications. Curr Med Chem. 2007;14(13):1437–57.
   PubMed Web of Science ®Google Scholar
• Wulff H, Miller MJ, Hansel W, et al. Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+ channel, IKCa1: a potential immunosuppressant. Proc Natl Acad Sci U S A. 2000;97(14):8151–6.
   PubMed Web of Science ®Google Scholar
• Christophersen P, Wulff H. Pharmacological gating modulation of small- and intermediate-conductance Ca2+-activated K+ channels (KCa2.x and KCa3.1). Channels (Austin). 2015;9(6):336–43.
   PubMed Web of Science ®Google Scholar
• Wulff H, Köhler R. Endothelial small-conductance and intermediate-conductance KCa channels: an update on their pharmacology and usefulness as cardiovascular targets. J Cardiovasc Pharmacol. 2013;61(2):102–12.
   PubMed Web of Science ®Google Scholar
• Wulff H, Zhorov BS. K+ channel modulators for the treatment of neurological disorders and autoimmune diseases. Chem Rev. 2008;108(5):1744–73.
   PubMed Web of Science ®Google Scholar
• Wulff H, Castle NA, Pardo LA. Voltage-gated potassium channels as therapeutic targets. Nat Rev Drug Discov. 2009;8(12):982–1001.
   PubMed Web of Science ®Google Scholar
• Wulff H, Pennington M. Targeting effector memory T-cells with Kv1.3 blockers. Curr Opin Drug Discov Devel. 2007;10(4):438–45.
   PubMed Web of Science ®Google Scholar
• Sankaranarayanan A, Raman G, Busch C, et al. 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. 2009;75(2):281–95.
   PubMed Web of Science ®Google Scholar
• Coleman N, Brown BM, Olivan-Viguera A, et al. New positive Ca2+-activated K+ channel gating modulators with selectivity for KCa3.1. Mol Pharmacol. 2014;86(3):342–57.
   PubMed Web of Science ®Google Scholar
• Brown BM, Shim H, Zhang M, et al. Structural Determinants for the Selectivity of the Positive KCa3.1 Gating Modulator 5-Methylnaphtho[2,1-d]oxazol-2-amine (SKA-121). Mol Pharmacol. 2017;92(4):469–480.
   PubMed Web of Science ®Google Scholar
• Mishra RC, Mitchell JR, Gibbons-Kroeker C, et al. A pharmacologic activator of endothelial KCa channels increases systemic conductance and reduces arterial pressure in an anesthetized pig model. Vascular Pharmacology. 2016;79:24–31.
   PubMed Web of Science ®Google Scholar
• Radtke J, Schmidt K, Wulff H, et al. Activation of KCa3.1 by SKA-31 induces arteriolar dilatation and lowers blood pressure in normo- and hypertensive connexin40-deficient mice. Br J Pharmacol. 2013;170(2):293–303.
   PubMed Web of Science ®Google Scholar
• Stocker M. Ca2+-activated K+ channels: molecular determinants and function of the SK family. Nat Rev Neurosci. 2004;5(10):758–70.
   PubMed Web of Science ®Google Scholar
• Kohler M, Hirschberg B, Bond CT, et al. Small-conductance, calcium-activated potassium channels from mammalian brain. Science. 1996;273(5282):1709–14.
   PubMed Web of Science ®Google Scholar
• Ishii TM, Silvia C, Hirschberg B, et al. A human intermediate conductance calcium-activated potassium channel. Proc Natl Acad Sci U S A. 1997;94(21):11651–6.
   PubMed Web of Science ®Google Scholar
• Fanger CM, Rauer H, Neben AL, et al. Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels. J Biol Chem. 2001;276(15):12249–56.
   PubMed Web of Science ®Google Scholar
• Yamniuk AP, Vogel HJ. Calmodulin's flexibility allow for promiscuity in its interactions with target proteins and pepRevtides. Molec Biotech. 2004;27:33–57.
   PubMed Web of Science ®Google Scholar
• Zhang M, Pascal JM, Schumann M, et al. Identification of the functional binding pocket for compounds targeting small-conductance Ca2+-activated potassium channels. Nat Commun. 2012;3:1021.
   PubMed Web of Science ®Google Scholar
• Zhang M, Pascal JM, Zhang JF. Unstructured to structured transition of an intrinsically disordered protein peptide in coupling Ca2+-sensing and SK channel activation. Proc Natl Acad Sci USA. 2013;110(12):4828–33.
   PubMed Web of Science ®Google Scholar
• Lam J, Wulff H. The Lymphocyte Potassium Channels Kv1.3 and KCa3.1 as Targets for Immunosuppression. Drug Dev Res. 2011;72(7):573–584.
   PubMed Web of Science ®Google Scholar
• Cahalan MD, Chandy KG. The functional network of ion channels in T lymphocytes. Immunol Rev. 2009;231(1):59–87.
   PubMedGoogle Scholar
• Coggins MP, Bloch KD. Nitric oxide in the pulmonary vasculature. Arterioscler Thromb Vasc Biol. 2007;27(9):1877–85.
   PubMed Web of Science ®Google Scholar
• Griffith TM.. Endothelium-dependent smooth muscle hyperpolarization: do gap junctions provide a unifying hypothesis? Br J Pharmacol. 2004;141(6):881–903.
   PubMed Web of Science ®Google Scholar
• Sandoo A, van Zanten JJ, Metsios GS, et al. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J. 2010;4:302–12.
   PubMedGoogle Scholar
• Mishra RC, Wulff H, Hill MA, et al. Inhibition of Myogenic Tone in Rat Cremaster and Cerebral Arteries by SKA-31, an Activator of Endothelial KCa2.3 and KCa3.1 Channels. J Cardiovasc Pharmacol. 2015;66(1):118–27.
   PubMed Web of Science ®Google Scholar
• Si H, Heyken WT, Wolfle SE, et al. Impaired endothelium-derived hyperpolarizing factor-mediated dilations and increased blood pressure in mice deficient of the intermediate-conductance Ca2+-activated K+ channel. Circulation Research. 2006;99(5):537–44.
   PubMed Web of Science ®Google Scholar
• Köhler R, Olivan-Viguera A, Wulff H. Endothelial Small- and Intermediate-Conductance K Channels and Endothelium-Dependent Hyperpolarization as Drug Targets in Cardiovascular Disease. Adv Pharmacol. 2016;77:65–104.
   PubMedGoogle Scholar
• Milkau M, Köhler R, de Wit C. Crucial importance of the endothelial K+ channel SK3 and connexin40 in arteriolar dilations during skeletal muscle contraction. FASEB J. 2010;24(9):3572–9.
   PubMed Web of Science ®Google Scholar
• Brahler S, Kaistha A, Schmidt VJ, et al. Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension. Circulation. 2009;119(17):2323–32.
   PubMed Web of Science ®Google Scholar
• Damkjaer M, Nielsen G, Bodendiek S, et al. Pharmacological activation of KCa3.1/KCa2.3 channels produces endothelial hyperpolarization and lowers blood pressure in conscious dogs. Br J Pharmacol. 2012;165(1):223–34.
   PubMed Web of Science ®Google Scholar
• Fliser D, Wiecek A, Suleymanlar G, et al. The dysfunctional endothelium in CKD and in cardiovascular disease: mapping the origin(s) of cardiovascular problems in CKD and of kidney disease in cardiovascular conditions for a research agenda. Kidney Int Suppl (2011). 2011;1(1):6–9.
   PubMed Web of Science ®Google Scholar
• Rajendran P, Rengarajan T, Thangavel J, et al. The vascular endothelium and human diseases. Int J Biol Sci. 2013;9(10):1057–69.
   PubMed Web of Science ®Google Scholar
• Ellinsworth DC, Sandow SL, Shukla N, et al. Endothelium-Derived Hyperpolarization and Coronary Vasodilation: Diverse and Integrated Roles of Epoxyeicosatrienoic Acids, Hydrogen Peroxide, and Gap Junctions. Microcirculation. 2016;23(1):15–32.
   PubMed Web of Science ®Google Scholar
• Anderson TJ, Charbonneau F, Title LM, et al. Microvascular function predicts cardiovascular events in primary prevention: long-term results from the Firefighters and Their Endothelium (FATE) study. Circulation. 2011;123(2):163–9.
   PubMed Web of Science ®Google Scholar
• Köhler R, Hoyer J. The endothelium-derived hyperpolarizing factor: insights from genetic animal models. Kidney Int. 2007;72(2):145–50.
   PubMed Web of Science ®Google Scholar
• Feigl EO. Coronary physiology. Physiol Rev. 1983;63(1):1–205.
   PubMed Web of Science ®Google Scholar
• Mishra RC, Belke D, Wulff H, et al. SKA-31, a novel activator of SK(Ca) and IK(Ca) channels, increases coronary flow in male and female rat hearts. Cardiovasc Res. 2013;97(2):339–48.
   PubMed Web of Science ®Google Scholar
• Kurian MM, Berwick ZC, Tune JD. Contribution of IKCa channels to the control of coronary blood flow. Exp Biol Med. 2011;236(5):621–7.
   Web of Science ®Google Scholar
• Tuteja D, Xu D, Timofeyev V, et al. Differential expression of small-conductance Ca2+-activated K+ channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes. Am J Physiol Heart Circ Physiol. 2005;289(6):H2714–23.
   PubMed Web of Science ®Google Scholar
• Xu Y, Tuteja D, Zhang Z, et al. Molecular identification and functional roles of a Ca2+-activated K+ channel in human and mouse hearts. J Biol Chem. 2003;278(49):49085–94.
   PubMed Web of Science ®Google Scholar
• Zhang XD, Lieu DK, Chiamvimonvat N. Small-conductance Ca2+-activated K+ channels and cardiac arrhythmias. Heart Rhythm. 2015;12(8):1845–51.
   PubMed Web of Science ®Google Scholar
• Faraci FM, Heistad DD. Regulation of the cerebral circulation: role of endothelium and potassium channels. Physiol. 1998;78(1):53–97.
   Google Scholar
• Cipolla MJ, Smith J, Kohlmeyer MM, et al. SKCa and IKCa Channels, myogenic tone, and vasodilator responses in middle cerebral arteries and parenchymal arterioles: effect of ischemia and reperfusion. Stroke. 2009;40(4):1451–7.
   PubMed Web of Science ®Google Scholar
• Hannah RM, Dunn KM, Bonev AD, et al. Endothelial SK(Ca) and IK(Ca) channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow. J Cereb Blood Flow Metab. 2011;31(5):1175–86.
   PubMed Web of Science ®Google Scholar
• Khaddaj Mallat R, Mathew John C, Kendrick DJ, et al. The vascular endothelium: A regulator of arterial tone and interface for the immune system. Crit Rev Clin Lab Sci. 2017;54(7-8):458–470.
   PubMed Web of Science ®Google Scholar
• Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial function in humans. Clin Sci. 2011;120(9):357–75.
   PubMed Web of Science ®Google Scholar
• Donato AJ, Morgan RG, Walker AE, et al. Cellular and molecular biology of aging endothelial cells. J Mol Cell Cardiol. 2015;89(Pt B):122–35.
   PubMedGoogle Scholar
• Hadi HA, Suwaidi JA. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag. 2007;3(6):853–76.
   PubMedGoogle Scholar
• Calles-Escandon J, Cipolla M. Diabetes and endothelial dysfunction: a clinical perspective. Endocrine Reviews. 2001;22(1):36–52.
   PubMed Web of Science ®Google Scholar
• Martin-Timon I, Sevillano-Collantes C, Segura-Galindo A, et al. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World J Diabetes. 2014;5(4):444–70.
   PubMedGoogle Scholar
• Arkin JM, Alsdorf R, Bigornia S, et al. Relation of cumulative weight burden to vascular endothelial dysfunction in obesity. Am J Cardiol. 2008;101(1):98–101.
   PubMed Web of Science ®Google Scholar
• Meyers MR, Gokce N. Endothelial dysfunction in obesity: etiological role in atherosclerosis. Curr Opin Endocrinol Diabetes Obes. 2007;14(5):365–9.
   PubMedGoogle Scholar
• Miller JD, Aronis KN, Chrispin J, et al. Obesity, Exercise, Obstructive Sleep Apnea, and Modifiable Atherosclerotic Cardiovascular Disease Risk Factors in Atrial Fibrillation. J Am Coll Cardiol. 2015;66(25):2899–2906.
   PubMed Web of Science ®Google Scholar
• Norata GD, Grigore L, Raselli S, et al. Post-prandial endothelial dysfunction in hypertriglyceridemic subjects: molecular mechanisms and gene expression studies. Atherosclerosis. 2007;193(2):321–7.
   PubMed Web of Science ®Google Scholar
• Steinberg HO, Chaker H, Leaming R, et al. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest. 1996;97(11):2601–10.
   Google Scholar
• Farb MG, Ganley-Leal L, Mott M, et al. Arteriolar function in visceral adipose tissue is impaired in human obesity. Arterioscler Thromb Vasc Biol. 2012;32(2):467–73.
   PubMed Web of Science ®Google Scholar
• de Jongh RT, Serne EH, RG IJ, et al. Impaired microvascular function in obesity: implications for obesity-associated microangiopathy, hypertension, and insulin resistance. Circulation. 2004;109(21):2529–35.
   PubMed Web of Science ®Google Scholar
• Verlohren S, Dubrovska G, Tsang SY, et al. Visceral periadventitial adipose tissue regulates arterial tone of mesenteric arteries. Hypertension. 2004;44(3):271–6.
   PubMed Web of Science ®Google Scholar
• Forstermann U, Munzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation. 2006;113(13):1708–14.
   PubMed Web of Science ®Google Scholar
• Lobato NS, Filgueira FP, Akamine EH, et al. Mechanisms of endothelial dysfunction in obesity-associated hypertension. Br J Med Biol Res. 2012;45(5):392–400.
   PubMed Web of Science ®Google Scholar
• Lobato NS, Filgueira FP, Akamine EH, et al. Obesity induced by neonatal treatment with monosodium glutamate impairs microvascular reactivity in adult rats: role of NO and prostanoids. Nutrition, Metabolism, and Cardiovascular Diseases. 2011;21(10):808–16.
   PubMed Web of Science ®Google Scholar
• Climent B, Moreno L, Martinez P, et al. Upregulation of SK3 and IK1 channels contributes to the enhanced endothelial calcium signaling and the preserved coronary relaxation in obese Zucker rats. PloS One. 2014;9(10):e109432.
   PubMed Web of Science ®Google Scholar
• Climent B, Simonsen U, Rivera L. Effects of obesity on vascular potassium channels. Curr Vasc Pharmacol. 2014;12(3):438–52.
   PubMed Web of Science ®Google Scholar
• Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109(23 Suppl 1):III27–32.
   PubMed Web of Science ®Google Scholar
• Mudau M, Genis A, Lochner A, et al. Endothelial dysfunction: the early predictor of atherosclerosis. Cardiovasc J Afr. 2012;23(4):222–31.
   PubMed Web of Science ®Google Scholar
• Shimokawa H.. Primary endothelial dysfunction: atherosclerosis. J Mol Cell Cardiol. 1999;31(1):23–37.
   PubMed Web of Science ®Google Scholar
• Bi D, Toyama K, Lemaitre V, et al. The intermediate conductance calcium-activated potassium channel KCa3.1 regulates vascular smooth muscle cell proliferation via controlling calcium-dependent signaling. J Biol Chem. 2013;288(22):15843–53.
   PubMed Web of Science ®Google Scholar
• Albarwani SA, Mansour F, Khan AA, et al. Aging Reduces L-Type Calcium Channel Current and the Vasodilatory Response of Small Mesenteric Arteries to Calcium Channel Blockers. Front Physiol. 2016;7:171.
   PubMed Web of Science ®Google Scholar
• Leung SW, Vanhoutte PM. Endothelium-dependent hyperpolarization: age, gender and blood pressure, do they matter? Acta Physiologica. 2017;219(1):108–123.
   PubMed Web of Science ®Google Scholar
• Cervantes Gracia K, Llanas-Cornejo D, Husi H. CVD and Oxidative Stress. J Clin Med. 2017;6(2):22.
   PubMed Web of Science ®Google Scholar
• Ungvari Z, Kaley G, de Cabo R, et al. Mechanisms of vascular aging: new perspectives. J Gerontol A Biol Sci Med Sci. 2010;65(10):1028–41.
   PubMed Web of Science ®Google Scholar
• Chennupati R, Lamers WH, Koehler SE, et al. Endothelium-dependent hyperpolarization-related relaxations diminish with age in murine saphenous arteries of both sexes. Br J Pharmacol. 2013;169(7):1486–99.
   PubMed Web of Science ®Google Scholar
• Behringer EJ, Shaw RL, Westcott EB, et al. Aging impairs electrical conduction along endothelium of resistance arteries through enhanced Ca2+-activated K+ channel activation. Arterioscler Thromb Vasc Biol. 2013;33(8):1892–901.
   PubMed Web of Science ®Google Scholar
• Bradding P, Wulff H. The K+ channels K(Ca)3.1 and K(v)1.3 as novel targets for asthma therapy. Br J Pharmacol. 2009;157(8):1330–9.
   PubMed Web of Science ®Google Scholar
• Soder RP, Parajuli SP, Hristov KL, et al. SK channel-selective opening by SKA-31 induces hyperpolarization and decreases contractility in human urinary bladder smooth muscle. Am J Physiol Regul Integr Comp Physiol. 2013;304(2):R155–63.
   PubMed Web of Science ®Google Scholar
• Parajuli SP, Soder RP, Hristov KL, et al. Pharmacological activation of small conductance calcium-activated potassium channels with naphtho[1,2-d]thiazol-2-ylamine decreases guinea pig detrusor smooth muscle excitability and contractility. J Pharmacol Exp Ther. 2012;340(1):114–23.
   PubMed Web of Science ®Google Scholar
• Shakkottai VG, do Carmo Costa M, Dell'Orco JM, et al. Early changes in cerebellar physiology accompany motor dysfunction in the polyglutamine disease spinocerebellar ataxia type 3. J Neurosci. 2011;31(36):13002–14.
   PubMed Web of Science ®Google Scholar