Abstract
The modulation of TREK-1 leak and Kv1.4 voltage-gated K+ channels by fatty acids and lysophospholipids was studied in bovine adrenal zona fasciculata (AZF) cells. In whole-cell patch-clamp recordings, arachidonic acid (AA) (1–20 µM) dramatically and reversibly increased the activity of bTREK-1, while inhibiting bKv1.4 current by mechanisms that occurred with distinctly different kinetics. bTREK-1 was also activated by the polyunsaturated cis fatty acid linoleic acid but not by the trans polyunsaturated fatty acid linolelaidic acid or saturated fatty acids. Eicosatetraynoic acid (ETYA), which blocks formation of active AA metabolites, failed to inhibit AA activation of bTREK-1, indicating that AA acts directly. Compared to activation of bTREK-1, inhibition of bKv1.4 by AA was rapid and accompanied by a pronounced acceleration of inactivation kinetics. Cis polyunsaturated fatty acids were much more effective than trans or saturated fatty acids at inhibiting bKv1.4. ETYA also effectively inhibited bKv1.4, but less potently than AA. bTREK-1 current was markedly increased by lysophospholipids including lysophosphatidyl choline (LPC) and lysophosphatidyl inositol (LPI). At concentrations from 1–5 µM, LPC produced a rapid, transient increase in bTREK-1 that peaked within one minute and then rapidly desensitized. The transient lysophospholipid-induced increases in bTREK-1 did not require the presence of ATP or GTP in the pipette solution. These results indicate that the activity of native leak and voltage-gated K+ channels are directly modulated in reciprocal fashion by AA and other cis unsaturated fatty acids. They also show that lysophospholipids enhance bTREK-1, but with a strikingly different temporal pattern. The modulation of native K+ channels by these agents differs from their effects on the same channels expressed in heterologous cells, highlighting the critical importance of auxiliary subunits and signaling. Finally, these results reveal that AZF cells express thousands of bTREK-1 K+ channels that lie dormant until activated by metabolites including phospholipase A2 (PLA2)-generated fatty acids and lysophospholipids. These metabolites may alter the electrical and secretory properties of AZF cells by modulating bTREK-1 and bKv1.4 K+ channels.
Similar content being viewed by others
References
H. Bang Y. Kim D. Kim (2000) ArticleTitleTREK-2, a new member of the mechanosensitive tandem-pore K+ channel family. J. Biol. Chem. 275 17412–17419 Occurrence Handle10.1074/jbc.M000445200 Occurrence Handle1:CAS:528:DC%2BD3cXktFaksL8%3D Occurrence Handle10747911
B.V. Bassa D.D. Roh N.D. Vaziri M.A. Kirschenbaum V.S. Kamanna (1999) ArticleTitleLysophosphatidylcholine activates mesangial cell PKC and MAP kinase by PLCgamma-1 and tyrosine kinase-Ras pathways. Am. J. Physiol. 277 F328–F337 Occurrence Handle1:CAS:528:DyaK1MXmt1GisL8%3D Occurrence Handle10484515
B.P. Bean (1984) ArticleTitleNitrendipine block of cardiac calcium channels: High affinity binding to the inactivated state. Proc. Natl. Acad. Sci. USA 81 6388–6392 Occurrence Handle6093100
S.P.J. Brooks K.B. Storey (1992) ArticleTitleBound and determined: a computer program for making buffers of defined ion concentrations. Anal. Biochem. 201 119–126 Occurrence Handle1:CAS:528:DyaK38Xht1Cgtr8%3D Occurrence Handle1621949
J. Capdevila L. Gil M. Orellana L.J. Marnett J.I. Mason P. Yadagiri J.R. Falck (1988) ArticleTitleInhibitors of cytochrome P-450-dependent arachidonic acid metabolism. Arch. Biochem. Biophys. 261 257–263 Occurrence Handle1:CAS:528:DyaL1cXkvVGqsro%3D Occurrence Handle3128168
C.M. Colbert E. Pan (1999) ArticleTitleArachidonic acid reciprocally alters the availability of transient and sustained dendritic K+ in hippocampal CA1 pyramidal neurons. J. Neurosci. 19 8163–8171 Occurrence Handle1:CAS:528:DyaK1MXmt1aqurw%3D Occurrence Handle10493718
C.B. Cymeryng C. Paz L. Dada M. Cornejo M.I. Neuman P.G. Mele C. Finkielstein A.R. Solano C.F. Mendez M. Park (1995) ArticleTitleACTH-dependent proteolytic activity of a novel phosphoprotein (p43) intermediary in the activation of phospholipase A2 and steroidogenesis. Endo. Res. 21 281–288 Occurrence Handle1:CAS:528:DyaK2MXmslamsL4%3D
F. Duprat F. Lesage A.J. Patel M. Fink G. Romey M. Lazdunski (2000) ArticleTitleThe neuroprotective agent riluzole activates the two P domain K+ channels TREK-1 and TRAAK. Mol. Pharmacol. 57 906–912 Occurrence Handle1:CAS:528:DC%2BD3cXjtVegur8%3D Occurrence Handle10779373
J.A. Enyeart L. Xu JJ. Enyeart (2000) ArticleTitleA bovine adrenocortical Kv1.4 K+ channel whose expression is potently inhibited by ACTH. J. Biol. Chem. 275 34640–34649 Occurrence Handle10.1074/jbc.M004214200 Occurrence Handle1:CAS:528:DC%2BD3cXotFWltLw%3D Occurrence Handle10913143
J.J. Enyeart J.C. Gomora L. Xu J.A. Enyeart (1997) ArticleTitleAdenosine triphosphate activates a noninactivating K+ current in adrenal cortical cells through nonhydrolytic binding. J. Gen. Physiol. 110 679–692 Occurrence Handle10.1085/jgp.110.6.679 Occurrence Handle1:CAS:528:DyaK2sXnvFGhs70%3D Occurrence Handle9382896
J.J. Enyeart B. Mlinar J.A. Enyeart (1993) ArticleTitleT-type Ca2+ channels are required for ACTH-stimulated cortisol synthesis by bovine adrenal zona fasciculate cells. Mol. Endo. 7 1031–1040 Occurrence Handle10.1210/me.7.8.1031 Occurrence Handle1:CAS:528:DyaK3sXmsVWlsbw%3D
J.J. Enyeart B. Mlinar J.A. Enyeart (1996) ArticleTitleAdrenocorticotropic hormone and cAMP inhibit noninactivating K+ current in adrenocortical cells by an A-kinase-independent mechanism requiring ATP hydrolysis. J. Gen. Physiol. 108 251–264 Occurrence Handle1:CAS:528:DyaK28XmsFCrs7k%3D Occurrence Handle8894975
J.J. Enyeart L. Xu S. Danthi J.A. Enyeart (2002) ArticleTitleAn ACTH- and ATP-regulated background K+ channel in adrenocortical cells is TREK-1. J. Biol. Chem. 211 49186–49199 Occurrence Handle10.1074/jbc.M207233200
J.J. Enyeart L. Xu J.C. Gomora J.A. Enyeart (2001.) ArticleTitleReciprocal modulation of voltage-gated and background K+ channels mediated by nucleotides and ACTH. Mol. Pharmacol. 60 114–123 Occurrence Handle1:CAS:528:DC%2BD3MXks1CrtLo%3D Occurrence Handle11408606
X. Fang S. Gibson M. Flowers T. Furui R.C.J. Bast G.B. Mills (1997) ArticleTitleLysophosphatidylcholine stimulates activator protein 1 and the c-Jun N-terminal kinase activity. J.Biol.Chem. 272 13683–13689 Occurrence Handle10.1074/jbc.272.21.13683 Occurrence Handle1:CAS:528:DyaK2sXjsFWhsLc%3D Occurrence Handle9153219
M. Fink F. Duprat F. Lesage R. Reyes G. Romey C. Heurteaux M. Lazdunski (1996) ArticleTitleCloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J. 15 6854–6862 Occurrence Handle1:CAS:528:DyaK2sXosFehtQ%3D%3D Occurrence Handle9003761
M. Fink F. Lesage F. Duprat C. Heurteaux R. Reyes M. Fosset M. Lazdunski (1998) ArticleTitleA neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. EMBO J. 17 3297–3308 Occurrence Handle10.1093/emboj/17.12.3297 Occurrence Handle1:CAS:528:DyaK1cXksFClt7g%3D Occurrence Handle9628867
J.C. Gomora JJ. Enyeart (1998) ArticleTitleCa2+ depolarizes adrenal cortical cells through selective inhibition of an ATP-activated K+ current. Am. J. Physiol. 275 C1526–C1537 Occurrence Handle1:CAS:528:DyaK1MXhsFGmug%3D%3D Occurrence Handle9843714
J.C. Gomora JJ. Enyeart (1999) ArticleTitleMibefradil potently blocks ATP-activated K+ channels in adrenal cells. Mol. Pharmacol. 56 1192–1197 Occurrence Handle1:CAS:528:DyaK1MXns1yhtLg%3D Occurrence Handle10570046
O.P. Hamill A. Marty E. Neher B. Sakmann F.J. Sigworth (1981) ArticleTitleImproved patch clamp techniques for high resolution current recording from cells and cell-free membrane patches. Pfluegers Arch. 391 85–100
B. Hille (2001) Ion Channels of Excitable Membranes. Sinauer Associates Sunderland, MA
M.H. Holmqvist J. Cao M.H. Knoppers M.E. Jurman P.S. Distefano K.J. Rhodes Y. Xie W.F. An (2001) ArticleTitleKinetic modulation of Kv4-mediated A-current by arachidonic acid is dependent on potassium channel interacting proteins. J. Neurosci. 21 4154–4161 Occurrence Handle1:CAS:528:DC%2BD3MXktlKlsrk%3D Occurrence Handle11404400
S. Keros C.J. McBain (1997) ArticleTitleArachidonic acid inhibits transient potassium currents and broadens action potentials during electrographic seizures in hippocampal pyramidal and inhibitory interneurons. J. Neurosci. 17 3476–3487 Occurrence Handle1:CAS:528:DyaK2sXjt1WltLo%3D Occurrence Handle9133373
D. Kim D.E. Clapham (1989) ArticleTitlePotassium channels in cardiac cells activated by arachindonic acid and phospholipids. Science 244 1174–1179 Occurrence Handle1:CAS:528:DyaL1MXksFCmurc%3D Occurrence Handle2727703
D. Kim C.D. Sladek C. Aguado-Velasco J.R. Mathiasen (1995) ArticleTitleArachidonic acid activation of a new family of K+ channels in cultured rat neuronal cells. J. Physiol. 484 643–660 Occurrence Handle1:CAS:528:DyaK2MXls1Ojsrs%3D Occurrence Handle7623282
I. Kojima K. Kojima H. Rasmussen (1985) ArticleTitlePossible role of phospholipase A2 action and arachidonic acid metabolism in angiotensin II-mediated aldosterone secretion. Endocrinology 117 1057–1066 Occurrence Handle1:CAS:528:DyaL2MXltlGnsrg%3D Occurrence Handle3926464
F. Lesage M. Lazdunski (2000) ArticleTitleMolecular and functional properties of two-pore-domain potassium channels. Am. J. Physio. 279 F793–F801 Occurrence Handle1:CAS:528:DC%2BD3cXotFartrw%3D
F. Maingret I. Lauritzen A.J. Patel C. Heurteaux R. Reyes F. Lesage M. Lazdunski E. Honore (2000) ArticleTitleTREK-1 is a heat-activated background K+ channel. EMBO J 19 2483–2491 Occurrence Handle10.1093/emboj/19.11.2483 Occurrence Handle1:CAS:528:DC%2BD3cXkslansbw%3D Occurrence Handle10835347
F. Maingret A.J. Patel F. Lesage M. Lazdunski E. Honore (2000) ArticleTitleLysophospholipids open the two-pore domain mechano-gated K+ channels TREK-1 and TRAAK. J. Biol. Chem. 275 10128–10133 Occurrence Handle10.1074/jbc.275.14.10128 Occurrence Handle1:CAS:528:DC%2BD3cXisFWjs7Y%3D Occurrence Handle10744694
B. Mlinar B.A. Biagi J.J. Enyeart (1993) ArticleTitleA novel K+ current inhibited by ACTH and Angiotensin II in adrenal cortical cells. J. Biol. Chem. 268 8640–8644 Occurrence Handle1:CAS:528:DyaK3sXit1Kju7k%3D Occurrence Handle8386167
B. Mlinar B.A. Biagi J.J. Enyeart (1995) ArticleTitleLosartan-sensitive AII receptors linked to depolarization- dependent cortisol secretion through a novel signaling pathway. J. Biol. Chem. 270 20942–20951 Occurrence Handle10.1074/jbc.270.36.20942 Occurrence Handle1:CAS:528:DyaK2MXnvFKmurg%3D Occurrence Handle7673118
B. Mlinar J.J. Enyeart (1993) ArticleTitleVoltage-gated transient currents in bovine adrenal fasciculata cells II: A-type K+ current. J. Gen. Physiol. 102 239–255 Occurrence Handle1:STN:280:ByuD2crlsFw%3D Occurrence Handle8228910
R.W. Ordway J.J. Singer J.V.J. Walsh (1991) ArticleTitleDirect regulation of ion channels by fatty acids. Trends Neurosci. 14 96–100 Occurrence Handle10.1016/0166-2236(91)90069-7 Occurrence Handle1:CAS:528:DyaK3MXktVehtbs%3D Occurrence Handle1709540
R.W. Ordway J.V. Walsh J.J. Singer (1989) ArticleTitleArachidonic acid and other fatty acids directly activate potassium channels in smooth muscle cells. Science 244 1176–1179 Occurrence Handle1:CAS:528:DyaL1MXkslGhtLY%3D Occurrence Handle2471269
A.J. Patel E. Honore (2001) ArticleTitleProperties and modulation of mammalian 2P domain K+ channels. Trends Neurosci. 24 339–346 Occurrence Handle10.1016/S0166-2236(00)01810-5 Occurrence Handle1:CAS:528:DC%2BD3MXjsFamu7s%3D Occurrence Handle11356506
A.J. Patel E. Honore F. Maingret F. Lesage M. Fink F. Duprat M. Lazdunski (1998) ArticleTitleA mammalian two pore domain mechano-gated S-like K+ channel. EMBO J 17 4283–4290 Occurrence Handle1:CAS:528:DyaK1cXlsFOltLw%3D Occurrence Handle9687497
R. Peri B.A. Wible A.M. Brown (2001) ArticleTitleMutations in the Kv beta 2 binding site for NADPH and their effects on Kv1.4. J. Biol. Chem. 276 738–741 Occurrence Handle10.1074/jbc.M008445200 Occurrence Handle1:CAS:528:DC%2BD3MXmtFWhsA%3D%3D Occurrence Handle11024060
C. Terrenoire I. Lauritzen F. Lesage GL. Romey M. Lazdunski (2001) ArticleTitleA TREK-1-like potassium channel in atrial cells inhibited by beta-adrenergic stimulation and activated by volatile anesthetics. Circ. Res. 89 336–342 Occurrence Handle1:CAS:528:DC%2BD3MXmsVeqs74%3D Occurrence Handle11509450
Y. Tian R.D. Smith T. Balla K.J. Catt (1998) ArticleTitleAngiotensin II activates mitogen-activated protein kinase via protein kinase C and Ras/Raf-1 kinase in bovine adrenal glomerulosa cells. Endocrinology 139 1801–1809 Occurrence Handle10.1210/en.139.4.1801 Occurrence Handle1:CAS:528:DyaK1cXitVKlsLk%3D Occurrence Handle9528965
A. Villarroel T.L. Schwarz (1996) ArticleTitleInhibition of the Kv4 (Shal) family of transient K+ currents by arachidonic acid. J. Neurosci. 16 2522–2532 Occurrence Handle1:CAS:528:DyaK28XitFKhur8%3D Occurrence Handle8786428
H. Wang S.W. Walker J.I. Mason S.D. Morley B.C. Williams (2000) ArticleTitleRole of arachidonic acid metabolism in ACTH-stimulated cortisol secretion by bovine adrenocortical cells. Endo. Res. 26 705–709 Occurrence Handle1:CAS:528:DC%2BD3MXotlKjsg%3D%3D
L. Xu J.J. Enyeart (2001) ArticleTitleProperties of ATP-dependent K+ channels in adrenocortical cells. Am. J. Physiol. 280 C199–C215 Occurrence Handle1:CAS:528:DC%2BD3MXjtVWmu70%3D
T. Yamazaki K. Higuchi S. Kominami S. Takemori (1996) ArticleTitle15-lipoxygenase metabolite(s) of arachidonic acid mediates adrenocorticotropin action in bovine adrenal steroidogenesis. Endocrinology 137 2670–2675 Occurrence Handle10.1210/en.137.7.2670 Occurrence Handle1:CAS:528:DyaK28XjvVWjsLo%3D Occurrence Handle8770885
Acknowledgements
This work was supported in part by National Institures of Health Grant R01DK47875 (to J.J.E) and in part by the National Science Foundation under Agreement 0112050 (S.D.).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Danthi, S., Enyeart, J. & Enyeart, J. Modulation of Native TREK-1 and Kv1.4 K+ Channels by Polyunsaturated Fatty Acids and Lysophospholipids . J. Membrane Biol. 195, 147–164 (2003). https://doi.org/10.1007/s00232-003-0616-0
Received:
Issue Date:
DOI: https://doi.org/10.1007/s00232-003-0616-0