Cardiovascular Research 1992;26:1017-1020

1017

Short review Modulation of ATP sensitive potassium channels J R de Weille

P

Regulation by nucleotides Intracellular nucleotides may either inhibit or activate KATP channels, depending on the species of nucleotide used, its concentration, the presence of Mg2’ ions, and the presence of other nucleotides that compete for the same binding sites on the channel.6 Most, if not all, interactions of nucleotides with the KATPchannel can be understood by the assumption that the channel has both a binding site that leads to channel inhibition and a separate binding site that leads to channel a~tivati0n.l~ Inhibition of KATPchannels by ATP does not require Mg2+ ions and non-hydrolysable ATP analogues are equally effective.6 l7 Other nucleotides such as ADP, GTP, and GDP

also inhibit the KATPchannel, albeit with lower efficacy and at higher concentration^."-^' The inhibitory action of ATP is reduced in the presence of ADP, an effect that can be explained partially by competition for the same inhibitory binding site. ADP and any other non-ATP nucleotides thus behave as partial agonists. In physiological conditions, the ratio of intracellular ATP/ADP is probably the important variable in KATPchannel regulation.6 In the absence of nucleotides, KATPchannel activity decreases gradually: it runs down. Channel activity returns if the intracellular face of the membrane is exposed for a minute to Mg-ATP followed by washout, a phenomenon that has been named “reactivation” or “refreshment”.22Channel refreshment does not occur if non-hydrolysable analogues are used or if Mg2+ is absent. These requirements might suggest channel phosphorylation. It has been shown indeed that KATPchannel activity in the p cell is modulated after stimulation of kinase C by phorbol esters or diacylglycerol.*’ 24 However, channel phosphorylation cannot be the mechanism involved in channel reactivation, as it has been shown that M ADP and fluorescein dyes also reactivate the channel. 8-19 21 Fluorescein dyes such as eosin are known to bind to the Mg-ATP site on sever$ ATPases. The Na’/K’-ATPase is the most studied example. Eosin and the sulphydryl reagent eosin maleimide were shown to inhibit its activity. Therefore, it seems that the KATPchannel possesses a second, activatory, binding site to which only hydrolysable nucleotides can bind if Mg2’ ions are present. Channel run down occumng upon removal of intracellular nucleotides would then be explained either by the slow dissociation of nucleotides from the activatory binding site or by a slow return from an activated conformational state, which might persist in the absence of nucleotides, to the ground state. In principle it is possible to choose between these alternatives, since dissociation kinetics should be a function of the ligand used. The most effective ligands to the activatory binding site, certainly in cardiac myocytes, appear to be dinucleotides, underlining the importance of ADP in KATPchannel regulation.

Inhibition by sulphonylureas Soon after the discovery of KATPchannels, it was shown that they could be inhibited by tolbutamide, one of the sulphonylureas that is used in the treatment of non-insulindependent diabetes.* The efficacies of various sulphonylureas, measured as the percentage of inhibition of Rb’ efflux

Institut de Pharmacologie MolCculaire et Cellulaire UPR 41 1, 660 route des Lucioles, Sophia-Antipolis, 06560 Valbonne, France: J R de Weille.

Downloaded from by guest on June 9, 2016

otassium channels that are sensitive to variations of intracellular ATP (KATP) are resent in various tissues: heart muscle,’ the pancreas,Pskeletal m ~ s c l e smooth ,~ muscle? and the central nervous ~ y s t e m The . ~ role of KATP channels is probably best understood in the pancreatic p cell, where these channels have bee; shown to mediate the glucose induced insulin secretion. If extracellular glucose is raised, the ratio of intracellular ATP over ADP is thought to increase slightly, inhibiting KATP channels and depolarising the plasma membrane, thereby increasing Ca2’ influx and the subsequent insulin release. Insulin secretion is also increased if KATPchannels are inhibited by antidiabetic sulphonylureas, some of which bind with high affinity to the channel.8 As sulphonylureas systematically inhibit KATP channels in excised patches, it is thought that the sulphonylurea receptor is located somewhere on the channel. For this reason, glibenclamide, a sulphonylurea that binds to the p cell KATPchannel with an affinity in the subnanomolar range,’ is often used to identify KATPchannels. In smooth muscle, KATPchannels might play an important role in controlling muscle tone by modulating steady state activity of voltage dependent Ca2’ channels in the threshold region of membrane potentials (-50 to -40 mV).” KATP channels in smooth muscle are the target of a heterogeneous class of vasorelaxant drugs, the K’ channel openers (KCO), including cromakalim, nicorandil, minoxidil sulphate, and diazoxide.” I2 Cromakalim, for example, has been shown to stimulate Rb’ efflux and/or induce relaxation in aorta, portal vein, and airway smooth muscle.ls16 Some of the properties of KATPchannels and their modulation by intracellular and extracellular factors will be discussed briefly below.

1018

de Weille

Activation by potassium channel openers Potassium channel openers have been developed to treat hypertension, asthma, and baldness." l 2 Their primary targets are smooth muscle K' channels, but their actions on other tissues were studied when it became known that the KATP channel might be involved. In RINm5F insulinoma cells, cromakalim (100 pM) was found to hyperpolarise the ce! membrane and to activate KATPchannels in excised patches. In pancreatic islets, however, only pinacidil (500 pM) and diazoxide (500 pM) induced an increase of Rb' e f f l ~ x , '39~ while cromakalim (250 pM), nicorandil (500 pM), and minoxidil sulphate (500 pM) had no effect or even inhibited Rb' outflow with a concomitant increase in insulin secretion.38 40 41 In the heart, intracellular ATP depletion leads to action potential shortening, which is restored to control by glibenclamide." Cromakalim (30 pM) induced similar effects to ATP depletion?2 indicating that cromakalim opens KATPchannels. Pinacidil (100 pM) and SR 44866 (50 pM) were shown to activate KATP channels in membrane patches.43 Hence, while KATPchannels in the heart are readily activated by potassium channel openers, the pancreatic KATPchannel is less sensitive. The potassium channel openers EMD 52692, cromakalirn; and RP 49356 activate KATPchannels in skeletal muscle. As well as the KATPchannel, a second ATP insensitive and sulphonylurea

insensitive outwardly rectifying K' channel was found to be activated by potassium channel openers. Pinacidil and RP 49356 were found to shift the half maximum ATP concentration for KATP channel inhibition to higher values?' 45 while conversely, intracellular ATP increases the half maximum concentration of RP 49356 for channel a~tivation.~'These data indicate an (allosteric) interaction between ATP binding site(s) and potassium channel opener binding site(s) on the KATPchannel. The properties of K' channels activated by potassium channel openers in smooth muscle vary considerably between preparations. An ATP sensitive and Ca" insensitive channel of 135 pS in mesenteric arteries is activated by cromakalim and pinacidil and inhibited by 1 pM gliben~lamide.~ The same preparation possesses a 20 pS glibenclamide sensitive K' channel that is activated by calcitonin gene related peptide (CGRP).32 In coronary arteries, a 30 pS ATP sensitive K' channel is activated by nicorandil and inhibited by 20 VM gliben~larnide.~~ 3s In the same preparation a 148 pS Ca-' dependent K' channel was shown to be inhibited by intracellular ATP." The 155 pS charybdotoxin sensitive K' channel in airway smooth muscle is also modulated by intracellular ATP." Unfortunately, it is not known at the present whether Ca" dependent K' channels in coronary arteries and airway smooth muscle have more properties in common with known KATPchannels, such as their sensitivity to sulphonylureas. Indirect inhibition of Ca" dependent K' channels by ATP, due to chelation of Ca" by the nucleotide, is not entirely ruled out as an explanation for the observed ATP sensitivity. Others have shown that potassium channel openers increase glibenclamide sensitive Rb' efflux from airway muscle and induce r e l a ~ a t i o n .A~ ~small 10 pS Ca2' and ATP sensitive K' channel in the portal vein is activated by nicorandil (500 P M ) . ~A~second, Ca2' insensitive, 15 pS K' channel in the portal vein is activated by pinacidil, provided Mg-GDP is present intracellularly.4yCromakalim relaxes this muscle and the relaxation is antagonised by glibenclamide in the p M rangean35 49 Cromakalim also relaxes noradrenaline contracted aortic smooth muscle and stimulates Rb' efflux." Nicorandil induces the same effects in the aorta, but besides a glibenclamide sensitive Rb' flux, nicorandil also stimulates a glibenclamide insensitive Rb' flux component.3' Clearly, potassium channel openers do not exclusively stimulate channels that are sensitive to ATP but have different effects on KATPchannels depending on the tissue at hand.

Functional role Although the role of KATPchannels as sensors of the energetic state in p cells and in glucose sensitive neurones in the hypothalamus can easily be understood, it is probably too simple and even incorrect if this view is generalised to include other tissues where this channel is present. In the p cell and heart muscle, the KATPchannel is largely inhibited by submillimolar concentrations of intracellular ATP and is therefore never very active in physiological conditions. In the p cell, KATPchannels effectively control the resting membrane potential because many of them are present (-5000 per cell) and notwithstanding their low probability of opening, they are virtually the only channels that open in resting conditions, thus mediating even the slightest variations of intracellular ATP.' l7 In ventricular myocytes, KATPchannels play no role of importance in normal resting conditions and the few KATPchannels that

Downloaded from by guest on June 9, 2016

from /3 cells, correlates very well with the binding affinities of these drugs to the same cells, suggesting a close relation between sulphonylurea receptors and the KATPchannel.' K+T!T'; channels are also present in heart muscle and the CNS.-' They are particularly abundant in the substantia nigra, where they are involved in both pre- and postsynaptic modulation of GABA-ergic transmission." The affinities of sulphonylureas to cardiac and CNS membrane receptors were shown to be almost identical to those determined for the p cell, suggesting that KATPchannels in these tissues might be very similar.-"7 29 30 In contrast, affinities of sulphonylureas for their receptors in hypothalamus, skeletal muscle, and most smooth muscle preparations are much lower for the p cell. For example, glibenclamide, which inhibits p cell KATPchannels with an ICSOvalue below 1 nM, is used in the pM range to inhibit KCO induced Rb' flux in 4 13 IS 31-35 various smooth muscle preparations. Glibenclamide binding to the KATPchannel is modulated by intracellular nucleotides. It was shown that Mg-ATP, but not free ATPc, increases the apparent dissociation constant for glibenclamide by 3.6- to 6-foli in p cells." Similar results were obtained in the CNS. In the latter system, dinucleotides, notably ADP, were found to inhibit glibenclamide binding as well. The inhibition of sulphonylurea binding by nucleotides is not competitive, since the dissociation constant does not increase proportionally with the Mg-ATP concentration, but saturates beyond 100 pM of Mg-ATP.36The fluorescein derivatives, phloxin B and rose bengal, also inhibit glibenclamide binding to p cell membranes." In inside out membrane patches, in which KATPchannels were irreversibly activated by treatment of the activatory nucleotide binding site with the sulphydryl reagent eosin maleimide and then exposed to a solution without nucleotides, 100 nM glibenclamide was unable to block channel opening, while in control patches 20 nM was sufficient. These data indicate that occupation of the activatory nucleotide binding site by Mg-ATP or dinucleotides allosterically reduces the binding affinities of sulphonylureas to the KATPchannel.

Modulation of ATP sensitive potassium channels

Received 15 June 1992; accepted 31 July 1992.

1 Noma A. ATP-regulated K' channels in cardiac muscle. Nature 1983;305: 159-64. 2 Cook DL, Hales N. Intracellular ATP directly blocks K' channels in pancreatic p-cells. Nature 1984;311:27 1-3. 3 Spruce AE, Standen NB, Stanfield PR. Voltage-dependent ATPsensitive potassium channels of skeletal muscle membrane. Nature 1985;316:736-8. 4 Standen NB, Quayle JM, Davies NW, Brayden JE, Huang Y, Nelson MT. Hyperpolarizing vasodilators activate ATP-sensitive K' channels in arterial smooth muscle. Science 1989;245: 177-80. 5 Ashford M, Boden PR, Treherne JM. Glucose-induced excitation of hypothalmic neurones is mediated by ATP-sensitive K' channels. Pfugers Arch I990;415:479-83. 6 Peterson OH, Dunne MI. Regulation of K' channels plays a crucial role in the control of insulin secretion. Pfliiaers Arch * 1989;414:SIl5-20. 7 Yao Nelson T. Gaines KL. Raian AS. Berg M. Bovd AE. Increased cyt'osolic calcium, a signal -for sulfonyclurea-silmulated insulin release from beta cells. J Biol Chem 1987;262:2608-12. 8 Sturgess N, Ashford MLJ, Cook DL, Hales CN. The sulfonylurea receptor may be an ATP-sensitive potassium channel. Luncef 1985:ii:474-5. 9 Schmid-Antomarchi H, de Weille JR, Fosset M, Lazdunski M. The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K' channel in insulin secreting cells. J Biol Chem 1987;262: 15840-4. 10 Nelson MT, Patlak JB, Worley JF, Standen NB. Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone. Am J Phvsiol 1990;259:C3-18. I I Quast U, Cook NS. Moving together: K' channel openers and ATP-sensitive K+ channels. Trends Phannacol Sci 1989;lO: 431-5. 12 Duty S,Weston AH. Potassium channel openers, pharmacological effects and future uses. Drugs 1990;40:785-91. 13 Bray K, Quast U. Tedisamil (KC 8857) differentially inhibits the %b' efflux-stimulating and vasorelaxant properties o f cromakalim. Eur J Pharmacol 1991;200: 163-5. 14 Cook NS, Quast U, Hof RP, Baumlin Y, Pally C. Similarities in the mechanism of action of two new vasodilator drugs: pinacidil and BRL 34915. J Cardiovasc Pharmacol 1988;11:90-99. 15 Buckingham RE, Hamilton TC, Howlett DR, Mootoo S, Wilson Campell. Inhibition by glibenclamide of the vasorelaxant action of cromakalim in the rat. Br J Pharmacol 1989;97:57-64. 16 Quast U. Effect of the K+ efflux stimulating vasodilator BRL 34915 on *6Rbt efflux and spontaneous activity in guinea-pig portal vein. Br J Pharmacol 1987;91:569-78. 17 de Weille JR, Lazdunski M. Regulation of the ATP-sensitive potassium channel. In: Narahashi T, ed. Ion channels, vol 2. New York: Plenum, 1990:205-22. 18 de Weille JR, Miiller M, Lazdunski M. Activation and inhibition of ATP-sensitive K' channels by fluorescein derivativies. J Biol Chem 1992;267:4557-63. 19 Findlay I. Effects of ADP upon the ATP-sensitive K' channel in rat ventricular myocytes. J Membr Biol 1988;101:83-92. 20 Spruce AE, Standen NB, Stanfield PR. Studies of the unitary properties of adenosine-5'-triphosphate-regulated potassium channels in frog. J Physiol (Lond) 1987;382:2 13-36. 21 Tung RT, Kurachi Y.On the mechanism of nucleotide diphosphate activation of the ATP-sensitive K' channel in ventricular cell of guinea-pig. J Physiol (Lond) 1991;437:239-56. 22 Findlay I, Dunne M. ATP maintains ATP-inhibited channels in an operational state. P'iigers Arch 1986;407:238-40. 23 de Weille JR, Schmid-Antomarchi H, Fosset M, Lazdunski M. Regulation of ATP-sensitive K' channels in insulinoma cells. Activation by somatostatin and kinase C, the role of CAMP.Proc Natl Acad Sci USA 1989;86:2971-5. 24 Ribalet B, Eddlestone GT, Ciani S. Metabolic regulation of the K(ATP) and a maxi-K(V) channel in the insulin-secreting RINmSF cell. J Gen Physiol 1988;92:219-37. 25 Skou JC, Esmann M. Eosin, a fluorescent probe of ATP binding to the (Na' + K')-ATPase. Biochim Biophys Acta 1981;647: 232-40. 26 Quasthoff S, Franke C, Hatt H, Richter-Turtur M. Two different types of potassium channels in human skeletal muscle activated by potassium channel openers. Neurosci Left 1990;119: 191-4. 27 Amoroso S, Schmid-Antomarchi H, Fosset M. Lazdunski M. Glucose, sulfonylureas, and neurotransmitter release: role of ATPsensitive Kt channels. Science 1990;247:8524. 28 Hausser MA, de Weille JR, Lazdunski M. Activation by cromakalim of pre- and post-synaptic ATP-sensitive K' channels in substantia nigra. Biochem Biophys Res Commun 199 1374: 909-14. 29 Fosset M, de Weille JR, Green RD, Schmid-Antomarchi H, Lazdunski M. Antidiabetic sulfonylureas control action potential

Downloaded from by guest on June 9, 2016

may open as a result of slight variations iy2 the ATP/ADP ratio therefore have no effect whatsoever. Cardiac KATP channels only start to contribute to the membrane potential if intracellular ATP concentrations are drastically decreased by ischaemia or anoxia, giving rise to both increased K' efflux into the interstitial space and action potential shortening." 42 It has been shown on the one hand that pretreatment of cardiac muscle with glibenclamide reduces K' outflow and arrhythmia during ischaemiasO'I while on the other hand pretreatment with potassium channel openers prior to an ischaemic period improves recovery and limits infarct size:2 s3 indicating that KATPchannels come into play in extreme conditions. Even so, it does not seem very likely that KATPchannels would only serve in these extreme conditions. Therefore functional roles other than as ATP sensors have been proposed. In both skeletal muscle54and heart muscle" KATPchannel activity has been shown to increase upon intracellular acidification. This could mean that during increased muscle exercise and consequent lowering of pH, KATPchannel induced hyperpolarisation could compensate for a decrease in electrical excitability and prevent spontaneous contractions from occurring. Several ATP modulated K' channels in smooth muscle might be Ca2+dependent as well. Intracellular ATP in airway smooth muscle increases the half maximum concentration of Ca2' for channel activation, a mechanism that may be there to control the energy expenditure associated with a recurrent rise in cytosolic calcium. Others have emphasised the point that KATPchannels are modulated by extracellular factors and should therefore be regarded as receptor controlled channels. KATPchannels in p cells are inhibited by vasopressin" and activated by galanid' 58 and s~matostatin,~~ hormones that are known to inhibit adenylate cyclase activity via the Gi protein. In the heart, the adenosine AI receptor is coupled to Gi protein. Stabilised proteins or activated mi subunits were found to activate KATPchannels in both ventricular myocytes and skeletal muscle.59M, In mesenteric arteries CGRP activates glibenclamide sensitive K' channels.32 In dopaminergic neurones in the substantia nigra, GABA was shown to activate a tolbutamide sensitive K ' current.61In the CNS as a whole, KATPchannels appear to be located mostly in synapses,6263 which suggests that they may be the targets of neuromodulating peptides. A still unidentified cerebral peptide interferes with glibenclamide binding to rat brain cortex membranes.@ The KATPchannel, at least in the p cell and the heart muscle, is also regulated by intracellular factors such as kinase C,2324 kinase Ab5and arachidonic acid.666' Hence it may be that in systems other than the p cell, ATP sensitivity of the KATPchannel contributes only to a minor extent to physiological function. Possibly the function of the channel is primarily to mediate extracellular signals. Clearly, much work remains to be done in order to understand the physiological role of all the different K' channels in smooth muscle that have been shown to be modulated by sulphonylureas and potassium channel openers. Once their endogenous effectors are known, new pharmacological tools might be suggested that will enable us, more than at present, to differentiate between the members of the class of K' channels that is now, possibly misleadingly, called KATP.

1019

1020

30

31

32 33 34 35 36

37

38 39

41 42 43 44

45 46 47

48

properties in heart cells via high affinity receptors that are linked to ATP-dependent K' channels. J Biol Chem 1988;263:79334. Gopalakrishnan M, Johnson DE, Janis RA, Triggle DJ. Characterization of binding of the ATP-sensitive potassium channel ligand, [3H)glyburide, to neuronal and muscle preparations. J Pharmacol Exp Ther 199 1 ;257:1 162-70. Kreye VAW, Lenz T, Theiss U. The dualistic mode of action of ice vasodilator drug, nicorandil, differentiated by glibenclamide in Rb flux studies in rabbit isolated vascular smooth muscle. N a r y Schmiedebergs Arch Pharmacol 199 1;343:70-5. Nelson MT, Huang Y, Brayden JE. Hescheler J, Standen NB. Arterial dilations in response to calcitonin gene-related peptide involve activation of K' channels. Nature 1990;344:770-3. Kajioka S, Oike M, Kitamura K. Nicorandil opens a calciumdependent potassium channel in smooth muscle cells of the rat portal vein. J Pharmucol Exp Ther 1990,254:905-13. Miyoshi Y, Nakaya Y, Wakatsuki T, et al. Endothelin blocks ATPsensitive K' channels and depolarizes smooth muscle cells of porcine coronary artery. Circ Res 1992;70:6 1 2 4 . Inoue 1, Nakaya Y, Nakaya S, Mori H. Extracellular Ca"-activated K channel in coronary artery smooth muscle cells and its role in vasodilation. FEBS Lett 1989;255:2814. Schwanstecher M, Loser S, Brandt Ch, Scheffer K, Rosenberg F, Panten U. Adenine nucleotide-induced inhibition of binding of sulphonylureas to their receptor in pancreatic islets. Br J Pharmacol 1992;105:531 4 . Dunne M, Yule DI, Gallacher DV, Peterson OH. Comparative study of the effects of cromakalim (BRL 34915) and diazoxide on membrane potential, [Ca"], and ATP-sensitive potassium currents in insulin-secreting cells. J Membr Biol 1990;114:5340. Plant TD, Ganino GM, Henquin JC. Comparison of the effects of putative activators of K' channels on pancreatic B-cell function. Pfiigers Arch 1989;414:S152-3. Lebrun P, Devreux V, Hermann M, Herchuelz A. Similarities between the effects of pinacidil and diazoxide on ionic and secretory events in rat pancreatic islets. J Pharmacol Exp Ther 1989;25010l1-7. Lebrun P, Antoine M-H. Devreux V, Hermanns6M, Herchuelz A. Paradoxical inhibitory effect of cromakalim on Rb outflow from pancreatic islet cells. J Pharmacol Exp Ther I990;255:948-53. Antoine M-H, Hermann M, Herchuelz A, Lebrun P. Ionic and secretory response of pancreatic islet cells to minoxidil sulfate. J Pharmacol Exp Ther 1991;258:286-303. Sanguinetti M, Scott AL, Zingaro GJ, Siegl PSK. BRL 34915 (cromakalim) activates ATP-sensitive K' current in cardiac muscle. Proc Nafl Acad Sci USA 1988;85:8360-4. Findlay I, Deroubaix E, Guiraudou P, Coraboeuf E. Effects of activation of ATP-sensitive K' channels in mammalian ventricular myocytes. Am J Physiol 1989;257:H1551-9. Fan Z, Nakayama K, Hiraoka M. Multiple actions of pinacidil on adenosine triphosphate-sensitive potassium channels in guinea-pig ventricular myocytes. J Physiol (Lond) I990:430:273-95. Thuringer D, Escande D. Apparent competition between ATP and the potassium channel opener RP 49356 on ATP-sensitive K' channels of cardiac myocytes. Mol Pharmacol 1989;36:897-902. Silberberg SD, van Breemen C. An ATP, calcium and voltagesensitive potassium channel in porcine coronary smooth muscle cells. Biochem Biophys Res Commun 1990;172:517-22. Groschner K, Silberberg SD, Gelband CH, van Breemen C. CaZ+activated K' channels in airway smooth muscle are inhibited by cytoplasmic adenosine triphosphate. PJIiigers Arch I99 l;417: 5 17-22. Longmore J, Bray KM, Weston AH. The contribution of Rbpermeable potassium channels to the relaxant and membrane hyperpolarizing actions of cromakalim, RP49356 and diazoxide in bovine tracheal smooth muscle. Br J Pharmaccil 199 I ;102: 979-85.

49 Kajioka S, Kitamura K, Kitamura H. Guanosine diphosphate activates an adenosine 5'-triphosphate-sensitive K' channel in the rabbit portal vein. J Physiol (hind) 1991;444:397418. 50 Kantor PF, Coetzee WA, Carmeliet EE, Dennis SC, Ouie LH. Reduction of ischemic K' loss and arrhythmias in rat h e a h . Circ Res 1990;66:478-85. 51 Wilde AAM, Escande D, Schumacher CA. et al. Potassium accumulation in the globally ischemic mammalian heart. Circ Res 1990;67:83543. 52 Auchampach JA, Maruyama M, Cavero I, Gross GJ. The new K+ channel ouener aurikalim (RP 5289 1 ) reduces exuerimental infarct size in dogs in thk absence of hemodynamic changes. J Pharmacol Exp Ther 1991;259:961-7. 53 Es'cande D, Cavero I. K' channel openers: moving toward cardioprotection via strengthening of a natural mechanism. Trends Pharmacol Sci 1992 (in press). 54 Davies NW. Modulation of ATP-sensitive K' channels in skeletal muscle by intracellular protons. Nature 1990;343:375-7. 55 Cuevas J, Bassett AL, Cameron JS, Furukawa T, Myerburg RJ, Kimura S. Effect of H' on ATP-regulated K' channels in feline ventricular myocytes. Am J Physiol 1991 ;261:H755-61. 56 Martin SC, Yule DI, Dunne MJ, Gallacher DV, Petersen OH. Vasopressin directly closes ATP-sensitive potassium channels evoking membranes depolarization and an increase in the free intracellular Cat concentration in insulin-secreting cells. EMBO J 1989;8:3595-9. 57 Dunne M, Bullet MJ, Guodong L, Wolheim CB, Petersen OH. Galanin activates nucleotide-dependent K' channels in insulinsecreting cells via a pertussis toxin-sensitive G-protein. EMBO J 1989;8:413-20. 58 de Weille JR, Schmid-Antomarchi H, Fosset M, Lazdunski M. ATP-sensitive K' channels that are blocked by sulfonylureas in insulin secreting cells are activated by galanin, a hyperglycemic hormone. Proc Nut1 Acad Sci USA I988;85:13 12-6. 59 Kirsch GE, Codina J, Birnbaumer L, Brown AM. Coupling of ATP-sensitive K ' channels to A l receptors by G proteins in rat ventricular myocytes. Am J Physiol 1990;259:H820-6. 60 Parent L, Coronado R. Reconstitution of the ATP-sensitive potassium channel channel of skeletal muscle. J Gen Physiol 1989;94:445-63. 61 Roeper J, Hainsworth AH, Ashcroft FM. Tolbutamide reverses membrane hyperpolarization induced by activation of DZreceptors and GABAA receptors in isolated substantia nigra neurones. PJIugers Arch 416:473-5. 62 Mourre C, Widmann C, Lazdunski M. Specific hippocampal lesions indicate the presence of sulfonylurea binding sites associated to ATP-sensitive K' channels both post-synaptically and on mossy fibers. Brain Res 1991;540:340-4. 63 Mourre C, Widmann C, Lazdunski M. Sulfonylurea binding sites associated with ATP-regulated K+ channels in the central nervous system: autoradiographic analysis of their distribution and ontogenesis, and of their localization in mutant mice cerebellum. Brain Res 1990;519:2943. 64 Virsolvy-Vergine A, Briick M, Dufour M, Cauvin A. Lupo B, Bataille D. An endogenous ligand for the central sulfonylurea receptor. FEBS Letr 1988;242:65-9. 65 Ribalet B, Ciani S, Eddlestone GT. ATP mediates both activation and inhibition of K(ATP) channel activity via CAMP-dependent protein kinase in insulin-secreting cell lines. J Gen Physiol 198994693-7 I 7. 66 Kim D, Duff RA. Regulation of K' channels in cardiac myocytes by free fatty acids. Circ Res 1990;67:104&6. 67 Muller M, Szewczyk A, de Weille JR, Lazdunski M. ATP-sensitive channels in insulinoma cells are activated by nonesterified fatty acids. Biochemistry 1992;31:4656-6 1.

Downloaded from by guest on June 9, 2016

40

de Weille

Modulation of ATP sensitive potassium channels.

Cardiovascular Research 1992;26:1017-1020 1017 Short review Modulation of ATP sensitive potassium channels J R de Weille P Regulation by nucleotid...
719KB Sizes 0 Downloads 0 Views