The Role of the Membrane Potential of Endothelial and Smooth Muscle Cells in the Regulation of Coronary Blood Flow

Membrane Potential of Coronary Endothelial and Smooth Muscle Cells. In the mammalian heart the supply of oxygen and energy‐rich substrates through the coronary arterioles is continuously adapted to the variations of cardiac work. The coronary resistance arteries and the surrounding myocardium form a functional unit with multiple interactions between coronary endothelial cells, smooth muscle cells, perivascular nerves, and cardiac muscle cells. We describe the mechanisms underlying the electrical and chemical communication between the different cell types, the ionic channels contributing to the resting potential of endothelial and smooth muscle cells, and the mechanisms responsible for modulation of the resting potential. The main conclusion of our analysis is that the membrane potential of coronary endothelial and smooth muscle cells is one of the major determinants of coronary blood flow, and that modulation of the membrane potential provides a way to dilate or constrict coronary resistance arteries. It is proposed that the membrane potential of the myo‐endothelial regulatory unit, i.e., of the endothelial cells and the underlying smooth muscle cells in the terminal arterioles, may function as an integrator of the numerous local and global vasodilator and constrictor signals that provide for the adaptation of coronary blood flow to the metabolic demands of the heart.

[1]  N. Standen,et al.  Noradrenaline contracts arteries by activating voltage-dependent calcium channels , 1988, Nature.

[2]  M. Lazdunski,et al.  A new type of amiloride-sensitive cationic channel in endothelial cells of brain microvessels. , 1989, The Journal of biological chemistry.

[3]  M. Kotlikoff,et al.  Receptor‐activated calcium influx in human airway smooth muscle cells. , 1991, The Journal of physiology.

[4]  P. Ellinor,et al.  cDNA cloning of a dihydropyridine-sensitive calcium channel from rat aorta. Evidence for the existence of alternatively spliced forms. , 1990, The Journal of biological chemistry.

[5]  F. Romano,et al.  The Antiadrenergic Actions of Adenosine in the Heart , 1987 .

[6]  S. Moncada,et al.  Nitric oxide: physiology, pathophysiology, and pharmacology. , 1991, Pharmacological reviews.

[7]  J. Bény Endothelial and smooth muscle cells hyperpolarized by bradykinin are not dye coupled. , 1990, The American journal of physiology.

[8]  F. Ashcroft,et al.  Properties and functions of ATP-sensitive K-channels. , 1990, Cellular signalling.

[9]  L. D. Partridge,et al.  Calcium-activated non-specific cation channels , 1988, Trends in Neurosciences.

[10]  Y. Nakaya,et al.  Endothelin blocks ATP-sensitive K+ channels and depolarizes smooth muscle cells of porcine coronary artery. , 1992, Japanese journal of pharmacology.

[11]  F. Curry,et al.  Modulation of venular microvessel permeability by calcium influx into endothelial cells , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  H. Gaub,et al.  Hydrodynamic hyperpolarization of endothelial cells. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M. Kotlikoff,et al.  Delayed rectifier potassium channels in canine and porcine airway smooth muscle cells. , 1992, The Journal of physiology.

[14]  M. Hori,et al.  Coronary Circulation , 1987, Developments in Cardiovascular Medicine.

[15]  W. Mason,et al.  Spatial dynamics of intracellular calcium in agonist-stimulated vascular smooth muscle cells. , 1990, The American journal of physiology.

[16]  C. Vandenberg Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Burnstock,et al.  Rapid release of endothelin and ATP from isolated aortic endothelial cells exposed to increased flow. , 1990, Biochemical and biophysical research communications.

[18]  G. Matthews,et al.  Regulation of calcium influx by second messengers in rat mast cells , 1988, Nature.

[19]  A. Marty,et al.  Ca-dependent K channels with large unitary conductance in chromaffin cell membranes , 1981, Nature.

[20]  P. Pacaud,et al.  Large conductance calcium‐activated non‐selective cation channel in smooth muscle cells isolated from rat portal vein. , 1991, The Journal of physiology.

[21]  J. Daut,et al.  Passive electrical properties and electrogenic sodium transport of cultured guinea‐pig coronary endothelial cells. , 1988, The Journal of physiology.

[22]  J. Schrader,et al.  Adenine nucleotide release from isolated perfused guinea pig hearts and extracellular formation of adenosine. , 1991, Circulation research.

[23]  F. Edwards,et al.  Inward rectification in rat cerebral arterioles; involvement of potassium ions in autoregulation. , 1988, The Journal of physiology.

[24]  P. Ganz,et al.  Reversible microcarrier-mediated junctional communication between endothelial and smooth muscle cell monolayers: an in vitro model of vascular cell interactions. , 1985, Laboratory investigation; a journal of technical methods and pathology.

[25]  M. Lazdunski,et al.  Molecular mechanism of action of the vasoconstrictor peptide endothelin. , 1988, Biochemical and biophysical research communications.

[26]  O. Petersen,et al.  Potassium selective ion channels in insulin-secreting cells: physiology, pharmacology and their role in stimulus-secretion coupling. , 1991, Biochimica et biophysica acta.

[27]  E. McLachlan,et al.  The effect of temperature on neuromuscular transmission in the main caudal artery of the rat. , 1988, The Journal of physiology.

[28]  U. Decking,et al.  Interstitial transudate concentration of adenosine and inosine in rat and guinea pig hearts. , 1988, The American journal of physiology.

[29]  G. Burnstock,et al.  Vascular control by purines with emphasis on the coronary system. , 1989, European heart journal.

[30]  N. Standen,et al.  Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. , 1989, Science.

[31]  G. Droogmans,et al.  Exchange characteristics of the noradrenaline‐sensitive calcium store in vascular smooth muscle cells or rabbit ear artery. , 1981, The Journal of physiology.

[32]  H. Kuriyama,et al.  Guanosine diphosphate activates an adenosine 5'‐triphosphate‐sensitive K+ channel in the rabbit portal vein. , 1991, The Journal of physiology.

[33]  J. Putney Capacitative calcium entry revisited. , 1990, Cell calcium.

[34]  H G Lloyd,et al.  Contribution of S-adenosylhomocysteine to cardiac adenosine formation. , 1989, Journal of molecular and cellular cardiology.

[35]  G. Edwards,et al.  Potassium channel modulation in rat portal vein by ATP depletion: a comparison with the effects of levcromakalim (BRL 38227) , 1992, British journal of pharmacology.

[36]  N. Standen,et al.  Voltage-dependent ATP-sensitive potassium channels of skeletal muscle membrane , 1985, Nature.

[37]  Permeability and Mg2+ blockade of histamine‐operated cation channel in endothelial cells of rat intrapulmonary artery. , 1992, The Journal of physiology.

[38]  E. Shibata,et al.  A voltage‐dependent potassium current in rabbit coronary artery smooth muscle cells. , 1991, The Journal of physiology.

[39]  O. Petersen,et al.  Intracellular ADP activates K+ channels that are inhibited by ATP in an insulin‐secreting cell line , 1986, FEBS letters.

[40]  Y. Takata,et al.  ATP-induced hyperpolarization of smooth muscle cells of the guinea-pig coronary artery. , 1980, The Journal of pharmacology and experimental therapeutics.

[41]  Y. Nakaya,et al.  Angiotensin II blocks ATP-sensitive K+ channels in porcine coronary artery smooth muscle cells. , 1991, Biochemical and biophysical research communications.

[42]  H. Matsuda,et al.  Open‐state substructure of inwardly rectifying potassium channels revealed by magnesium block in guinea‐pig heart cells. , 1988, The Journal of physiology.

[43]  J. Pearson,et al.  Regulation of P2y‐purinoceptor‐mediated prostacyclin release from human endothelial cells by cytoplasmic calcium concentration , 1988, British journal of pharmacology.

[44]  D. A. Brown,et al.  Membrane current responses of NG108‐15 mouse neuroblastoma x rat glioma hybrid cells to bradykinin. , 1988, The Journal of physiology.

[45]  M. Lazdunski,et al.  Vasopressin modulates the spontaneous electrical activity in aortic cells (line A7r5) by acting on three different types of ionic channels. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[46]  S. Lax,et al.  Recessus und Bursae synoviales an den Lumbo-sakralgelenken , 1992 .

[47]  A. Henderson,et al.  Stimulus-secretion coupling in vascular endothelial cells. , 1990, Annual review of physiology.

[48]  N. Standen,et al.  Block of calcium-activated potassium channels in mammalian arterial myocytes by tetraethylammonium ions. , 1991, The American journal of physiology.

[49]  G. Dusting,et al.  Hyperpolarization and relaxation of arterial smooth muscle caused by nitric oxide derived from the endothelium , 1990, Nature.

[50]  J. Stull,et al.  GTP gamma S-dependent regulation of smooth muscle contractile elements. , 1992, The American journal of physiology.

[51]  N. Standen,et al.  The voltage‐dependent block of ATP‐sensitive potassium channels of frog skeletal muscle by caesium and barium ions. , 1988, The Journal of physiology.

[52]  D. Harder Pressure‐Dependent Membrane Depolarization in Cat Middle Cerebral Artery , 1984, Circulation research.

[53]  J. Brayden Hyperpolarization and relaxation of resistance arteries in response to adenosine diphosphate. Distribution and mechanism of action. , 1991, Circulation research.

[54]  G. Burnstock,et al.  A Dual Function for Adenosine 5′‐Triphosphate in the Regulation of Vascular Tone: Excitatory Cotransmitter with Noradrenaline from Perivascular Nerves and Locally Released Inhibitory Intravascular Agent , 1986, Circulation research.

[55]  R. Berne The role of adenosine in the regulation of coronary blood flow. , 1980, Circulation research.

[56]  L. Ignarro Biosynthesis and metabolism of endothelium-derived nitric oxide. , 1990, Annual review of pharmacology and toxicology.

[57]  R. Penner,et al.  Depletion of intracellular calcium stores activates a calcium current in mast cells , 1992, Nature.

[58]  M. Welsh,et al.  Calcium‐activated potassium channels in canine airway smooth muscle. , 1986, The Journal of physiology.

[59]  J. Bény,et al.  Dye and electrical coupling of endothelial cells in situ. , 1989, Tissue & cell.

[60]  A. Bakhramov,et al.  Histamine‐induced inward currents in cultured endothelial cells from human umbilical vein , 1988, British journal of pharmacology.

[61]  G. Osol,et al.  Effects of Diltiazem on Myogenic Tone in Pressurized Brain Arteries from Spontaneously Hypertensive Rats , 1986 .

[62]  J B Patlak,et al.  Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone. , 1990, The American journal of physiology.

[63]  F. Edwards,et al.  Sympathetic neuroeffector transmission in arteries and arterioles. , 1989, Physiological reviews.

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

[65]  R. Busse,et al.  Hyperpolarization and increased free calcium in acetylcholine-stimulated endothelial cells. , 1988, The American journal of physiology.

[66]  B. Fleischmann,et al.  Receptor-activated Ca influx in human airway smooth muscle: use of Ca imaging and perforated patch-clamp techniques. , 1993, The American journal of physiology.

[67]  M. Cannell,et al.  Bradykinin‐evoked changes in cytosolic calcium and membrane currents in cultured bovine pulmonary artery endothelial cells. , 1989, The Journal of physiology.

[68]  K. Krause,et al.  "Calciosome," a cytoplasmic organelle: the inositol 1,4,5-trisphosphate-sensitive Ca2+ store of nonmuscle cells? , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[69]  J. Rhodin,et al.  The ultrastructure of mammalian arterioles and precapillary sphincters. , 1967, Journal of ultrastructure research.

[70]  U. Quast,et al.  Moving together: K+ channel openers and ATP-sensitive K+ channels. , 1989, Trends in pharmacological sciences.

[71]  W. Schilling,et al.  Characterization of the bradykinin-stimulated calcium influx pathway of cultured vascular endothelial cells. Saturability, selectivity, and kinetics. , 1989, The Journal of biological chemistry.

[72]  David John Adams,et al.  Ion channels and regulation of intracellular calcium in vascular endothelial cells , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[73]  M. Nelson,et al.  Dihydropyridine inhibition of single calcium channels and contraction in rabbit mesenteric artery depends on voltage. , 1989, The Journal of physiology.

[74]  Simard Jm Calcium channel currents in isolated smooth muscle cells from the basilar artery of the guinea pig. , 1991 .

[75]  R. Berne Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow. , 1963, The American journal of physiology.

[76]  J. Putney,et al.  A model for receptor-regulated calcium entry. , 1986, Cell calcium.

[77]  J. Stull,et al.  Phosphorylation of myosin light chain kinase by the multifunctional calmodulin-dependent protein kinase II in smooth muscle cells. , 1992, The Journal of biological chemistry.

[78]  G. Burnstock,et al.  Endothelial cells cultured from human umbilical vein release ATP, substance P and acetylcholine in response to increased flow , 1990, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[79]  S S Segal,et al.  Conduction of vasomotor responses in arterioles: a role for cell-to-cell coupling? , 1989, The American journal of physiology.

[80]  K. Dellsperger,et al.  Role of ATP-sensitive potassium channels in coronary microvascular autoregulatory responses. , 1991, Circulation research.

[81]  T. Bolton,et al.  Calcium currents in single isolated smooth muscle cells from the rabbit ear artery in normal‐calcium and high‐barium solutions. , 1988, The Journal of physiology.

[82]  H. Matsuda,et al.  Single inwardly rectifying potassium channels in cultured muscle cells from rat and mouse. , 1989, The Journal of physiology.

[83]  R. Jacob,et al.  Agonist‐stimulated divalent cation entry into single cultured human umbilical vein endothelial cells. , 1990, The Journal of physiology.

[84]  F. Mekata The role of hyperpolarization in the relaxation of smooth muscle of monkey coronary artery. , 1986, The Journal of physiology.

[85]  O. A. Cabello,et al.  Depletion of the inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ store in vascular endothelial cells activates the agonist-sensitive Ca(2+)-influx pathway. , 1992, The Biochemical journal.

[86]  T. Itoh,et al.  Membrane hyperpolarization inhibits agonist‐induced synthesis of inositol 1,4,5‐trisphosphate in rabbit mesenteric artery. , 1992, Japanese journal of pharmacology.

[87]  Toshio Kitazawa,et al.  G-protein-mediated Ca2+ sensitization of smooth muscle contraction through myosin light chain phosphorylation. , 1991, The Journal of biological chemistry.

[88]  G. Giménez-Gallego,et al.  Purification and characterization of a unique, potent, peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus. , 1990, The Journal of biological chemistry.

[89]  F. Edwards,et al.  Inward rectification in submucosal arterioles of guinea‐pig ileum. , 1988, The Journal of physiology.

[90]  M. Berridge Inositol trisphosphate and calcium signalling , 1993, Nature.

[91]  A. Takai,et al.  Regulation of Ca2+ -dependent K+ -channel activity in tracheal myocytes by phosphorylation , 1989, Nature.

[92]  J. L. Gordon Extracellular ATP: effects, sources and fate. , 1986, The Biochemical journal.

[93]  K. Sanders,et al.  G proteins mediate suppression of Ca2+-activated K current by acetylcholine in smooth muscle cells. , 1989, The American journal of physiology.

[94]  G. C. Wellman,et al.  Endothelium-Dependent Dilation of Feline Cerebral Arteries: Role of Membrane Potential and Cyclic Nucleotides , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[95]  J. Daut,et al.  Hypoxic vasodilatation in isolated, perfused guinea‐pig heart: an analysis of the underlying mechanisms. , 1991, The Journal of physiology.

[96]  C. Garland,et al.  Evidence that nitric oxide does not mediate the hyperpolarization and relaxation to acetylcholine in the rat small mesenteric artery , 1992, British journal of pharmacology.

[97]  Single calcium channel currents of arterial smooth muscle at physiological calcium concentrations. , 1992, The American journal of physiology.

[98]  P. Davies,et al.  Haemodynamic shear stress activates a K+ current in vascular endothelial cells , 1988, Nature.

[99]  K. Magleby,et al.  Calcium-activated potassium channels , 1987, Trends in Neurosciences.

[100]  Arthur C. Guyton,et al.  Handbook of Physiology—The Cardiovascular System , 1985 .

[101]  T. Bolton,et al.  Calcium‐activated potassium channels in single smooth muscle cells of rabbit jejunum and guinea‐pig mesenteric artery. , 1986, The Journal of physiology.

[102]  M. Bond,et al.  Inositol trisphosphate-induced calcium release and contraction in vascular smooth muscle. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[103]  S. Sage,et al.  Electrical properties of resting and acetylcholine‐stimulated endothelium in intact rat aorta. , 1993, The Journal of physiology.

[104]  J. Schrader,et al.  Cardiac adenosine production is linked to myocardial pO2. , 1991, Journal of molecular and cellular cardiology.

[105]  J. Connat,et al.  An electron-microscopic study of smooth muscle cell dye coupling in the pig coronary arteries. Role of gap junctions. , 1992, Circulation research.

[106]  K. Magleby,et al.  Single channel recordings of Ca2+-activated K+ currents in rat muscle cell culture , 1981, Nature.

[107]  D. J. Wilkinson,et al.  Cholinergic modulation of apical Na+ channels in turtle colon: analysis of CDPC-induced fluctuations. , 1990, The American journal of physiology.

[108]  M. Oike,et al.  Endothelin augments unitary calcium channel currents on the smooth muscle cell membrane of guinea‐pig portal vein. , 1990, The Journal of physiology.

[109]  R. Irvine ‘Quanta’ Ca2+ release and the control of Ca2+ entry by inositol phosphates ‐ a possible mechanism , 1990, FEBS letters.

[110]  R. Coronado,et al.  Reconstitution of the ATP-sensitive potassium channel of skeletal muscle. Activation by a G protein-dependent process , 1989, The Journal of general physiology.

[111]  D. Clapham,et al.  Muscarinic‐Activated K+ Current in Bovine Aortic Endothelial Cells , 1988, Circulation research.

[112]  B. Nilius,et al.  Shear stress‐induced calcium transients in endothelial cells from human umbilical cord veins. , 1992, The Journal of physiology.

[113]  Y. E. Goldman,et al.  Kinetics of smooth and skeletal muscle activation by laser pulse photolysis of caged inositol 1,4,5-trisphosphate , 1987, Nature.

[114]  W. Large,et al.  Modulation of noradrenaline‐induced membrane currents by papaverine in rabbit vascular smooth muscle cells. , 1991, The Journal of physiology.

[115]  T. Rink,et al.  Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers? , 1987, Nature.

[116]  David John Adams,et al.  Calcium entry through receptor-operated channels in bovine pulmonary artery endothelial cells. , 1987, Tissue & cell.

[117]  J. Angus,et al.  Evidence that acetylcholine‐mediated hyperpolarization of the rat small mesenteric artery does not involve the K+ channel opened by cromakalim , 1991, British journal of pharmacology.

[118]  H. Dietrich,et al.  Capillary as a communicating medium in the microvasculature. , 1992, Microvascular research.

[119]  R. Popp,et al.  A calcium and ATP sensitive nonselective cation channel in the antiluminal membrane of rat cerebral capillary endothelial cells. , 1992, Biochimica et biophysica acta.

[120]  G. Isenberg,et al.  Contribution of two types of calcium channels to membrane conductance of single myocytes from guinea‐pig coronary artery. , 1990, The Journal of physiology.

[121]  Geoffrey Burnstock,et al.  Roles of P2‐Purinoceptors in the Cardiovascular System , 1991, Circulation.

[122]  P. Vanhoutte,et al.  Hyperpolarization as a mechanism for endothelium‐dependent relaxations in the porcine coronary artery. , 1992, The Journal of physiology.

[123]  R. Berne,et al.  Heterogeneity and sampling volume dependence of epicardial adenosine concentrations. , 1992, Journal of molecular and cellular cardiology.

[124]  R. Latorre,et al.  Reconstitution in planar lipid bilayers of a Ca2+-dependent K+ channel from transverse tubule membranes isolated from rabbit skeletal muscle. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[125]  T. Hallam,et al.  Influx of bivalent cations can be independent of receptor stimulation in human endothelial cells. , 1989, The Biochemical journal.

[126]  J. Pearson,et al.  Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides , 1979, Nature.

[127]  T. Hallam,et al.  Evidence that agonists stimulate bivalent-cation influx into human endothelial cells. , 1988, The Biochemical journal.

[128]  A. Szent-Györgyi,et al.  The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart 1 , 1929, The Journal of physiology.

[129]  Y. Ito,et al.  Effects of acetylcholine and catecholamines on the smooth muscle cell of the porcine coronary artery. , 1979, The Journal of physiology.

[130]  J. Bény,et al.  Interaction of bradykinin and des-Arg9-bradykinin with isolated pig coronary arteries: mechanical and electrophysiological events , 1987, Regulatory Peptides.

[131]  D. Williams,et al.  Guanosine 5'-monophosphate modulates gating of high-conductance Ca2+-activated K+ channels in vascular smooth muscle cells. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[132]  D. Kunze,et al.  Bradykinin‐Induced Increases in Cytosolic Calcium and Ionic Currents in Cultured Bovine Aortic Endothelial Cells , 1987, Circulation research.

[133]  T. Bolton,et al.  Two components of potassium current activated by depolarization of single smooth muscle cells from the rabbit portal vein. , 1989, The Journal of physiology.

[134]  G. Isenberg,et al.  Contribution of Ca(2+)‐induced Ca2+ release to the [Ca2+]i transients in myocytes from guinea‐pig urinary bladder. , 1992, The Journal of physiology.

[135]  P. Davies Vascular cell interactions with special reference to the pathogenesis of atherosclerosis. , 1986, Laboratory investigation; a journal of technical methods and pathology.

[136]  C. Y. Kao,et al.  Permeation, selectivity, and blockade of the Ca2+-activated potassium channel of the guinea pig taenia coli myocyte , 1989, The Journal of general physiology.

[137]  J. Daut,et al.  Sustained Hyperpolarization of Cultured Guinea Pig Coronary Endothelial Cells Induced by Adenosine , 1992, Journal of cardiovascular pharmacology.

[138]  I. Sweet,et al.  Comprehensive model of transport and metabolism of adenosine and S-adenosylhomocysteine in the guinea pig heart. , 1992, Circulation research.

[139]  N. Standen,et al.  Arterial dilations in response to calcitonin gene-related peptide involve activation of K+ channels , 1990, Nature.

[140]  H. Dietrich,et al.  Microvascular flow response to localized application of norepinephrine on capillaries in rat and frog skeletal muscle. , 1992, Microvascular research.

[141]  P. Ouyang,et al.  Blockade of the ATP-sensitive potassium channel modulates reactive hyperemia in the canine coronary circulation. , 1991, Circulation research.

[142]  R. Latorre,et al.  Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle , 1985, Nature.

[143]  L. Toro,et al.  U46619, a thromboxane A2 agonist, inhibits KCa channel activity from pig coronary artery. , 1992, The American journal of physiology.

[144]  M. Kotlikoff,et al.  Muscarinic inhibition of single KCa channels in smooth muscle cells by a pertussis-sensitive G protein. , 1991, The American journal of physiology.

[145]  J. Daut,et al.  Effects of vasoactive agonists on the membrane potential of cultured bovine aortic and guinea‐pig coronary endothelium. , 1991, The Journal of physiology.

[146]  U. Quast,et al.  In vitro and in vivo comparison of two K+ channel openers, diazoxide and cromakalim, and their inhibition by glibenclamide. , 1989, The Journal of pharmacology and experimental therapeutics.

[147]  J. R. Greenwell,et al.  Intracellular calcium 'signatures' evoked by different agonists in isolated bovine aortic endothelial cells. , 1992, Cell calcium.

[148]  Y. Nakaya,et al.  Extracellular Ca2+‐activated K channel in coronary artery smooth muscle cells and its role in vasodilation , 1989, FEBS letters.

[149]  R Latorre,et al.  Varieties of calcium-activated potassium channels. , 1989, Annual review of physiology.

[150]  P. Hatt,et al.  Regional capillary supply in the normal and hypertrophied rat heart. , 1980, Microvascular research.

[151]  B. Fredholm,et al.  How does adenosine inhibit transmitter release? , 1988, Trends in pharmacological sciences.

[152]  H. Bardenheuer,et al.  Relationship between Myocardial Oxygen Consumption, Coronary Flow, and Adenosine Release in an Improved Isolated Working Heart Preparation of Guinea Pigs , 1983, Circulation research.

[153]  J. Bassingthwaighte Interstitial adenosine: the measurement, the interpretation. , 1992, Journal of molecular and cellular cardiology.

[154]  P. Johnson,et al.  Autoregulation of Blood Flow , 1963, Science.

[155]  J. Daut,et al.  The electrical response of cultured guinea‐pig coronary endothelial cells to endothelium‐dependent vasodilators. , 1990, The Journal of physiology.

[156]  T. DeCoursey,et al.  Intrinsic gating of inward rectifier in bovine pulmonary artery endothelial cells in the presence or absence of internal Mg2+ , 1990, The Journal of general physiology.

[157]  K. Sanders,et al.  Ca2+-activated K channels of canine colonic myocytes. , 1989, The American journal of physiology.

[158]  B. Cox,et al.  Demonstration of vasorelaxant activity with an A1-selective adenosine agonist in porcine coronary artery: involvement of potassium channels. , 1992, The Journal of pharmacology and experimental therapeutics.

[159]  M. Nelson,et al.  Regulation of arterial tone by activation of calcium-dependent potassium channels. , 1992, Science.

[160]  R. Balaban,et al.  ATP-sensitive potassium channel is essential to maintain basal coronary vascular tone in vivo. , 1992, The American journal of physiology.

[161]  D. Cook,et al.  Intracellular ATP directly blocks K+ channels in pancreatic B-cells , 1984, Nature.

[162]  A. W. Jones,et al.  Stimulation of arterial 42K efflux by ATP depletion and cromakalim is antagonized by glyburide. , 1991, The American journal of physiology.

[163]  G. Burnstock,et al.  Different P2-purinergic receptor subtypes of endothelium and smooth muscle in canine blood vessels. , 1987, The Journal of pharmacology and experimental therapeutics.

[164]  D. Clapham,et al.  Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca2+-permeable channel , 1992, Nature.

[165]  M. Smith,et al.  Coronary reactive hyperemia and adenosine-induced vasodilation are mediated partially by a glyburide-sensitive mechanism. , 1992, Pharmacology.

[166]  L. Gray,et al.  Lymphocyte adhesion can be regulated by cytoskeleton-associated, PMA-induced capping of surface receptors. , 1992, The American journal of physiology.

[167]  B Sakmann,et al.  Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea‐pig heart. , 1984, The Journal of physiology.

[168]  M. Kotlikoff,et al.  Control of resting membrane potential by delayed rectifier potassium currents in ferret airway smooth muscle cells. , 1993, The Journal of physiology.

[169]  A. Brown,et al.  Coupling of ATP-sensitive K+ channels to A1 receptors by G proteins in rat ventricular myocytes. , 1990, The American journal of physiology.

[170]  S S Segal,et al.  Propagation of vasomotor responses coordinates arteriolar resistances. , 1989, The American journal of physiology.

[171]  J. Daut,et al.  Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels. , 1990, Science.

[172]  E. Shibata,et al.  Calcium currents in isolated rabbit coronary arterial smooth muscle myocytes. , 1990, The Journal of physiology.