Potassium channels on smooth muscle as a molecular target for plant-derived Resveratrol.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a phytoalexin present in a variety of plant species. Resveratrol has a wide spectrum of pharmacologic properties, and it exhibits versatile biological effects on different human and animal models. The studies have shown that potassium (K) channels can be potential targets in the mechanism of resveratrol action. K channels play a crucial role in maintaining membrane potential. Inhibition of K channels causes membrane depolarization and then contraction of smooth muscles, while the activation leads to membrane hyperpolarization and subsequently, relaxation. Five diverse types of K channels have been identified in smooth muscle cells in different tissue: ATP-sensitive K channels (KATP), voltage-dependent K channels (Kv), Ca2+ - and voltage-dependent K channels (BKCa), inward rectifier K channels (Kir), and tandem two-pore K channels (K2P). The expression and activity of K channels altered in many types of diseases. Aberrant function or expression of K channels can be underlying in pathologies such as cardiac arrhythmia, diabetes mellitus, hypertension, preterm birth, preeclampsia, and various types of cancer. Modulation of K channel activity by molecular approaches and selective drug development may be a novel treatment modality for these dysfunctions in the future. The plant-derived non-toxic polyphenols, such as resveratrol, can alter K channel activity and lead to the desired outcome. This review presents the basic properties, physiological, pathophysiological functions of K channels, and pharmacological roles of resveratrol on the major types of K channels that have been determined in smooth muscle cells.

[1]  B. Salehi,et al.  Therapeutic Applications of Curcumin Nanomedicine Formulations in Cardiovascular Diseases , 2020, Journal of clinical medicine.

[2]  Peng Ye,et al.  Potassium Channels in the Vascular Diseases , 2018, Vascular Biology - Selection of Mechanisms and Clinical Applications.

[3]  J. Rajkovic,et al.  Effect of gestational diabetes mellitus and pregnancy-induced hypertension on human umbilical vein smooth muscle KATP channels. , 2019, Experimental and molecular pathology.

[4]  S. Leung,et al.  Vascular adenosine monophosphate‐activated protein kinase: Enhancer, brake or both? , 2019, Basic & Clinical Pharmacology & Toxicology.

[5]  O. Yildiz,et al.  Potassium channels in vascular smooth muscle: a pathophysiological and pharmacological perspective , 2019, Fundamental & clinical pharmacology.

[6]  J. Rajkovic,et al.  The red wine polyphenol resveratrol induced relaxation of the isolated renal artery of diabetic rats: The role of potassium channels , 2019, Journal of Functional Foods.

[7]  A. Mishra,et al.  Resveratrol: A Double-Edged Sword in Health Benefits , 2018, Biomedicines.

[8]  Shu-Leei Tey,et al.  Mechanism of resveratrol-induced relaxation of the guinea pig fundus. , 2018, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[9]  F. Lasitschka,et al.  Role of ATP-sensitive potassium channels on hypoxic pulmonary vasoconstriction in endotoxemia , 2018, Respiratory Research.

[10]  Qianyun Feng,et al.  Maternal resveratrol consumption and its programming effects on metabolic health in offspring mechanisms and potential implications , 2018, Bioscience reports.

[11]  N. Tsoukias,et al.  The yin and yang of KV channels in cerebral small vessel pathologies , 2018, Microcirculation.

[12]  Xiaoping Lei,et al.  Resveratrol as a potential therapeutic drug for respiratory system diseases , 2017, Drug design, development and therapy.

[13]  I. Milosavljević,et al.  The red wine polyphenol, resveratrol improves hemodynamics, oxidative defence and aortal structure in essential and malignant hypertension , 2017 .

[14]  E. Nalivaiko,et al.  Resveratrol restores uterine contractions during hypoxia by blockade of ATP-sensitive potassium channels , 2017 .

[15]  Tuong-Vi Nguyen,et al.  Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction – implications as a preeclampsia treatment , 2017, Scientific Reports.

[16]  Shu-Leei Tey,et al.  Mechanism of resveratrol-induced relaxation in the human gallbladder , 2017, BMC Complementary and Alternative Medicine.

[17]  N. Tykocki,et al.  Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles. , 2017, Comprehensive Physiology.

[18]  D. Warburton,et al.  Inhaled resveratrol treatments slow ageing-related degenerative changes in mouse lung , 2017, Thorax.

[19]  Leonard K. Kaczmarek,et al.  International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels , 2017, Pharmacological Reviews.

[20]  H. Uzun,et al.  Endothelial Dysfunction and Hypertension. , 2016, Advances in experimental medicine and biology.

[21]  Wen-Xie Xu,et al.  Regulation of myometrial contraction by ATP-sensitive potassium (KATP) channel via activation of SUR2B and Kir 6.2 in mouse , 2016, The Journal of veterinary medical science.

[22]  Hussein N. Rubaiy The therapeutic agents that target ATP-sensitive potassium channels , 2016, Acta pharmaceutica.

[23]  Haixia Huang,et al.  Advanced Glycation End Products Impair Voltage-Gated K+ Channels-Mediated Coronary Vasodilation in Diabetic Rats , 2015, PloS one.

[24]  Chung-Pin Li,et al.  High Blood Pressure and All-Cause and Cardiovascular Disease Mortalities in Community-Dwelling Older Adults , 2015, Medicine.

[25]  N. Weissmann,et al.  Oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction , 2015, European Respiratory Journal.

[26]  V. Schini-Kerth,et al.  Role of AMP-activated Protein Kinase in NO- and EDHF-mediated Endothelium-dependent Relaxations to Red Wine Polyphenols. , 2015, Indian journal of physiology and pharmacology.

[27]  T. Gudermann,et al.  AMPK Dilates Resistance Arteries via Activation of SERCA and BKCa Channels in Smooth Muscle , 2015, Hypertension.

[28]  B. Ivković,et al.  Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium. , 2015, Molecular human reproduction.

[29]  N. MacAulay,et al.  PKC and AMPK regulation of Kv1.5 potassium channels , 2015, Channels.

[30]  L. Gojkovic-Bukarica,et al.  The Role of Potassium Channels in the Vasodilatation Induced by Resveratrol and Naringenin in Isolated Human Umbilical Vein , 2015, Drug development research.

[31]  Li-xue Zhang,et al.  Resveratrol and genistein inhibition of rat isolated gastrointestinal contractions and related mechanisms. , 2014, World journal of gastroenterology.

[32]  P. Koulen,et al.  Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance , 2014, Molecules.

[33]  W. Beierwaltes,et al.  Resveratrol induces acute endothelium-dependent renal vasodilation mediated through nitric oxide and reactive oxygen species scavenging. , 2014, American journal of physiology. Renal physiology.

[34]  A. Fenning,et al.  Effects of Resveratrol and Nebivolol on Isolated Vascular and Cardiac Tissues from Young Rats , 2014, Advances in pharmacological sciences.

[35]  S. Dalaklıoğlu,et al.  Role of different types of potassium channels in the relaxation of corpus cavernosum induced by resveratrol , 2014, Pharmacognosy magazine.

[36]  R. Novakovic,et al.  The effect of resveratrol on contractility of non-pregnant rat uterus: the contribution of K(+) channels. , 2013, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[37]  R. Novakovic,et al.  Cardiovascular effects of resveratrol. , 2013, Vojnosanitetski Pregled.

[38]  C. Sena,et al.  Endothelial dysfunction - a major mediator of diabetic vascular disease. , 2013, Biochimica et biophysica acta.

[39]  R. Novakovic,et al.  Effect of Wine Polyphenol Resveratrol on the Contractions Elicited Electrically or by Norepinephrine in the Rat Portal Vein , 2013, Phytotherapy Research.

[40]  K. Thakali,et al.  Ion channel remodeling in vascular smooth muscle during hypertension: Implications for novel therapeutic approaches. , 2013, Pharmacological research.

[41]  A. Jovanovic,et al.  KATP channels are up-regulated with increasing age in human myometrium , 2013, Mechanisms of Ageing and Development.

[42]  J. Carvalho-de-Souza,et al.  BK Channels in Cardiovascular Diseases and Aging. , 2013, Aging and disease.

[43]  M. Shen,et al.  The vasorelaxing effect of resveratrol on abdominal aorta from rats and its underlying mechanisms. , 2013, Vascular pharmacology.

[44]  F. Lang,et al.  Downregulation of Kv1.5 K+ Channels by the AMP-Activated Protein Kinase , 2012, Cellular Physiology and Biochemistry.

[45]  B. Thjódleifsson,et al.  Natural History of Irritable Bowel Syndrome in Women and Dysmenorrhea: A 10-Year Follow-Up Study , 2012, Gastroenterology research and practice.

[46]  Chun Jiang,et al.  K(ATP) channel action in vascular tone regulation: from genetics to diseases. , 2012, Sheng li xue bao : [Acta physiologica Sinica].

[47]  U. Förstermann,et al.  Cardiovascular effects and molecular targets of resveratrol. , 2012, Nitric oxide : biology and chemistry.

[48]  S. Olesen,et al.  AMP‐Activated Protein Kinase Downregulates Kv7.1 Cell Surface Expression , 2012, Traffic.

[49]  F. Lang,et al.  Downregulation of Kv 1 . 5 K + Channels by the AMP-Activated Protein Kinase , 2012 .

[50]  A. Mori,et al.  Resveratrol prevents bradykinin-induced contraction of rat urinary bladders by decreasing prostaglandin production and calcium influx. , 2011, European journal of pharmacology.

[51]  N. Holstein-Rathlou,et al.  Closure of multiple types of K+ channels is necessary to induce changes in renal vascular resistance in vivo in rats , 2011, Pflügers Archiv - European Journal of Physiology.

[52]  B. Kemp,et al.  Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase. , 2011, Biochemical and biophysical research communications.

[53]  Kai-Lee Wang,et al.  Effects of resveratrol, a grape polyphenol, on uterine contraction and Ca²+ mobilization in rats in vivo and in vitro. , 2011, Endocrinology.

[54]  Karen Brown,et al.  Clinical trials of resveratrol , 2011, Annals of the New York Academy of Sciences.

[55]  K. Dharmashankar,et al.  Vascular Endothelial Function and Hypertension: Insights and Directions , 2010, Current hypertension reports.

[56]  A. Mathie,et al.  SYMPOSIUM REVIEW: Gating of two pore domain potassium channels , 2010, The Journal of physiology.

[57]  Jin Han,et al.  Pathophysiology of voltage-gated K+ channels in vascular smooth muscle cells: modulation by protein kinases. , 2010, Progress in biophysics and molecular biology.

[58]  T. Flagg,et al.  Muscle KATP channels: recent insights to energy sensing and myoprotection. , 2010, Physiological reviews.

[59]  D. Sept,et al.  An Epilepsy/Dyskinesia-Associated Mutation Enhances BK Channel Activation by Potentiating Ca2+ Sensing , 2010, Neuron.

[60]  Péter Enyedi,et al.  Molecular Background of Leak K (cid:1) Currents: Two-Pore Domain Potassium Channels , 2010 .

[61]  Kazuharu Furutani,et al.  Inwardly rectifying potassium channels: their structure, function, and physiological roles. , 2010, Physiological reviews.

[62]  Michel Félétou,et al.  EDHF: an update. , 2009, Clinical science.

[63]  S. Dkhar,et al.  Potassium channels in health, disease & development of channel modulators. , 2009, The Indian journal of medical research.

[64]  C. Nichols,et al.  Molecular biology of KATP channels and implications for health and disease , 2009, IUBMB life.

[65]  J. Cui,et al.  Molecular mechanisms of BK channel activation , 2009, Cellular and Molecular Life Sciences.

[66]  M. Bumbasirevic,et al.  A role of ion channels in the endothelium-independent relaxation of rat mesenteric artery induced by resveratrol. , 2008, Journal of pharmacological sciences.

[67]  Hongfang Li,et al.  Inhibitory effects of genistein and resveratrol on guinea pig gallbladder contractility in vitro. , 2008, World journal of gastroenterology.

[68]  Aaron Schindeler,et al.  Seminars in cell & developmental biology. , 2008, Seminars in cell & developmental biology.

[69]  R. Warth,et al.  Physiology and pathophysiology of potassium channels in gastrointestinal epithelia. , 2008, Physiological reviews.

[70]  L. Pirola,et al.  Resveratrol: One molecule, many targets , 2008, IUBMB life.

[71]  B. Aggarwal,et al.  Resveratrol: A multitargeted agent for age-associated chronic diseases , 2008, Cell cycle.

[72]  L. Kuo,et al.  Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: role of nitric oxide and potassium channels. , 2007, Investigative ophthalmology & visual science.

[73]  R. Novakovic,et al.  The effect of potassium channel opener pinacidil on the non-pregnant rat uterus. , 2007, Basic & Clinical Pharmacology & Toxicology.

[74]  L. Chuang,et al.  Resveratrol enhances insulin secretion by blocking K(ATP) and K(V) channels of beta cells. , 2007, European journal of pharmacology.

[75]  V. Korovkina,et al.  Potassium channels and uterine function. , 2007, Seminars in cell & developmental biology.

[76]  B. Viollet,et al.  Activation of AMP kinase alpha1 subunit induces aortic vasorelaxation in mice. , 2007, The Journal of physiology.

[77]  C. Carlotti,et al.  Endothelium dysfunction caused by acute pressure distension of human saphenous vein used for myocardial revascularization. , 2007, Revista brasileira de cirurgia cardiovascular : orgao oficial da Sociedade Brasileira de Cirurgia Cardiovascular.

[78]  M. Breschi,et al.  Functional contribution of the endothelial component to the vasorelaxing effect of resveratrol and NS 1619, activators of the large-conductance calcium-activated potassium channels , 2007, Naunyn-Schmiedeberg's Archives of Pharmacology.

[79]  A. Novaković,et al.  Potassium channels-mediated vasorelaxation of rat aorta induced by resveratrol. , 2006, Basic & clinical pharmacology & toxicology.

[80]  N. Teramoto Physiological roles of ATP‐sensitive K+ channels in smooth muscle , 2006, The Journal of physiology.

[81]  E. Demirel‐Yilmaz,et al.  Resveratrol decreases calcium sensitivity of vascular smooth muscle and enhances cytosolic calcium increase in endothelium. , 2006, Vascular pharmacology.

[82]  S. Aşlamacı,et al.  Effects of resveratrol on vascular tone and endothelial function of human saphenous vein and internal mammary artery. , 2005, International journal of cardiology.

[83]  A. Terzic,et al.  K(ATP) channel therapeutics at the bedside. , 2005, Journal of molecular and cellular cardiology.

[84]  R. Aldrich,et al.  International Union of Pharmacology. LII. Nomenclature and Molecular Relationships of Calcium-Activated Potassium Channels , 2005, Pharmacological Reviews.

[85]  Ivano Morelli,et al.  Vasorelaxing effects of flavonoids: investigation on the possible involvement of potassium channels , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[86]  L. Santana,et al.  Downregulation of the BK Channel &bgr;1 Subunit in Genetic Hypertension , 2003, Circulation research.

[87]  F. Ashcroft,et al.  Potassium channel regulation , 2003, EMBO reports.

[88]  G. Saade,et al.  Effects of L-type Ca(2+)-channel blockade, K(+)(ATP)-channel opening and nitric oxide on human uterine contractility in relation to gestational age and labour. , 2003, Molecular human reproduction.

[89]  K. Magleby,et al.  Slo1 Tail Domains, but Not the Ca2+ Bowl, Are Required for the β1 Subunit to Increase the Apparent Ca2+ Sensitivity of BK Channels , 2002, The Journal of general physiology.

[90]  J. Morrison,et al.  Expression of mRNA transcripts for ATP-sensitive potassium channels in human myometrium. , 2002, Molecular human reproduction.

[91]  U. Förstermann,et al.  Resveratrol, a Polyphenolic Phytoalexin Present in Red Wine, Enhances Expression and Activity of Endothelial Nitric Oxide Synthase , 2002, Circulation.

[92]  Richard W. Aldrich,et al.  Coupling between Voltage Sensor Activation, Ca2+ Binding and Channel Opening in Large Conductance (BK) Potassium Channels , 2002, The Journal of general physiology.

[93]  E. Roche,et al.  Nuclear KATP channels trigger nuclear Ca2+ transients that modulate nuclear function , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[94]  V. Korovkina,et al.  Molecular Diversity Of Vascular Potassium Channel Isoforms , 2002, Clinical and experimental pharmacology & physiology.

[95]  A. El-Mowafy Resveratrol activates membrane-bound guanylyl cyclase in coronary arterial smooth muscle: a novel signaling mechanism in support of coronary protection. , 2002, Biochemical and biophysical research communications.

[96]  J. Leiro,et al.  The possible implication of trans-Resveratrol in the cardioprotective effects of long-term moderate wine consumption. , 2002, Molecular pharmacology.

[97]  Yongge Liu,et al.  Pharmacological comparison of native mitochondrial K(ATP) channels with molecularly defined surface K(ATP) channels. , 2001, Molecular pharmacology.

[98]  E. Naderali,et al.  The mechanism of resveratrol-induced vasorelaxation differs in the mesenteric resistance arteries of lean and obese rats. , 2001, Clinical science.

[99]  Christopher Miller An overview of the potassium channel family , 2000, Genome Biology.

[100]  F. Vogalis Potassium channels in gastrointestinal smooth muscle. , 2000, Journal of autonomic pharmacology.

[101]  P. Pagel,et al.  Sarcolemmal and Mitochondrial Adenosine Triphosphate– dependent Potassium Channels: Mechanism of Desflurane-induced Cardioprotection , 2000, Anesthesiology.

[102]  S. Chen,et al.  Evidence for the stimulatory effect of resveratrol on Ca(2+)-activated K+ current in vascular endothelial cells. , 2000, Cardiovascular research.

[103]  Y. Kurachi,et al.  Molecular aspects of ATP-sensitive K+ channels in the cardiovascular system and K+ channel openers. , 2000, Pharmacology & therapeutics.

[104]  W. Jackson Ion channels and vascular tone. , 2000, Hypertension.

[105]  E. Chien,et al.  Expression of adenosine triphosphate-sensitive potassium channel subunits in female rat reproductive tissues: overlapping distribution of messenger ribonucleic acid for weak inwardly rectifying potassium channel subunit 6.1 and sulfonylurea-binding regulatory subunit 2. , 1999, American journal of obstetrics and gynecology.

[106]  F. Rosenfeldt,et al.  Pharmacology of coronary artery bypass grafts. , 1999, The Annals of thoracic surgery.

[107]  E. Aiello,et al.  Role of a Ca2+-activated K+ current in the maintenance of resting membrane potential of isolated, human, saphenous vein smooth muscle cells , 1999, Pflügers Archiv.

[108]  N. Rusch,et al.  Increased expression of Ca2+-sensitive K+ channels in aorta of hypertensive rats. , 1997, Hypertension.

[109]  J. Monsuez,et al.  Cardiac potassium currents and channels--part I: basic science aspects. , 1997, International journal of cardiology.

[110]  N. Standen,et al.  ATP-sensitive and inwardly rectifying potassium channels in smooth muscle. , 1997, Physiological reviews.

[111]  S. Archer,et al.  Potassium channel diversity in vascular smooth muscle cells. , 1997, Canadian journal of physiology and pharmacology.

[112]  J. Martens,et al.  Alterations in rat interlobar artery membrane potential and K+ channels in genetic and nongenetic hypertension. , 1996, Circulation research.

[113]  C. Pace-Asciak,et al.  Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta. , 1996, General pharmacology.

[114]  F. Ashcroft,et al.  Promiscuous coupling between the sulphonylurea receptor and inwardly rectifying potassium channels , 1996, Nature.

[115]  M. Nelson,et al.  Physiological roles and properties of potassium channels in arterial smooth muscle. , 1995, The American journal of physiology.

[116]  M. Kotlikoff,et al.  Role of G proteins and KCa channels in the muscarinic and beta-adrenergic regulation of airway smooth muscle. , 1995, The American journal of physiology.

[117]  N. Standen,et al.  KATP channels in vascular smooth muscle. , 1994, Cardiovascular research.

[118]  N. Rusch,et al.  Remission of high blood pressure reverses arterial potassium channel alterations. , 1994, Hypertension.

[119]  S. Renaud,et al.  Wine, alcohol, platelets, and the French paradox for coronary heart disease , 1992, The Lancet.

[120]  N. Standen,et al.  Role of potassium channels in the vascular response to endogenous and pharmacological vasodilators. , 1991, Blood vessels.

[121]  Y. Nishizuka Studies and perspectives of protein kinase C. , 1986, Science.

[122]  J P Cazenave,et al.  The effects of flavonoids on cyclic nucleotide phosphodiesterases. , 1986, Progress in clinical and biological research.

[123]  B. S. Pallotta Calcium‐activated potassium channels in rat muscle inactivate from a short‐duration open state. , 1985, The Journal of physiology.

[124]  K. Johnson An Update. , 1984, Journal of food protection.

[125]  A. Noma,et al.  ATP-regulated K+ channels in cardiac muscle , 1983, Nature.

[126]  R. Keynes The ionic channels in excitable membranes. , 1975, Ciba Foundation symposium.