TASK1 and TASK3 Potassium Channels: Determinants of Aldosterone Secretion and Adrenocortical Zonation

Abstract

Potassium channels control the membrane voltage of aldosterone-producing zona glomerulosa cells. They are responsible for the unique K⁺ sensitivity of these cells and are important molecular targets of angiotensin II signaling. Among the 78 pore-forming K⁺ channels in human genome only a few are found in adrenal glands. The 2-P-domain K⁺ channels TASK1 and TASK3 are strongly expressed in the adrenal cortex and produce a background K⁺ conductance, which is pivotal for the regulation of the aldosterone secretion in zona glomerulosa cells. Disruption of the TASK1 gene in mice resulted in an autonomous aldosterone production and caused a remarkable aberrant expression of aldosterone synthase in zona fasciculata cells that normally produce glucocorticoids. After puberty, only in male mice aldosterone production was switched off in the zona fasciculata and regular zonation of aldosterone synthase occurred. In double mutant TASK1 ^–/– /TASK3 ^–/– mice, also adult male mice displayed primary hyperaldosteronism. Therefore, these knockout mice are interesting models to study mechanisms of autonomous aldosterone production and adrenocortical zonation. These data suggest that modifications of the adrenocortical K⁺ conductances could also contribute to autonomic aldosterone production and primary hyperaldosteronism in humans.

K2P - KCNK2 - KCNK3 - KCNK9 - adrenocortical zonation - aldosterone - angiotensin II - adrenal cortex

References

• 1 Willenberg HS, Schinner S, Ansurudeen I. New mechanisms to control aldosterone synthesis.  Horm Metab Res. 2008;  40 435-441
• 2 Spat A, Hunyady L. Control of aldosterone secretion: a model for convergence in cellular signaling pathways.  Physiol Rev. 2004;  84 489-539
• 3 Bassett MH, White PC, Rainey WE. The regulation of aldosterone synthase expression.  Mol Cell Endocrinol. 2004;  217 67-74
• 4 Cherradi N, Brandenburger Y, Rossier MF, Vallotton MB, Stocco DM, Capponi AM. Atrial natriuretic peptide inhibits calcium-induced steroidogenic acute regulatory protein gene transcription in adrenal glomerulosa cells.  Mol Endocrinol. 1998;  12 962-972
• 5 Ganz MB, Nee JJ, Isales CM, Barrett PQ. Atrial natriuretic peptide enhances activity of potassium conductance in adrenal glomerulosa cells.  Am J Physiol. 1994;  266 C1357-C1365
• 6 Spat A. Glomerulosa cell – a unique sensor of extracellular K+ concentration.  Mol Cell Endocrinol. 2004;  217 23-26
• 7 Lotshaw DP. Role of membrane depolarization and T-type Ca2+ channels in angiotensin II and K+ stimulated aldosterone secretion.  Mol Cell Endocrinol. 2001;  175 157-171
• 8 Liu H, Enyeart JA, Enyeart JJ. Angiotensin II inhibits native bTREK-1 K+ channels through a PLC-, kinase C-, and PIP2-independent pathway requiring ATP hydrolysis.  Am J Physiol Cell Physiol. 2007;  293 C682-C695
• 9 Chen X, Talley EM, Patel N, Gomis A, McIntire WE, Dong B, Viana F, Garrison JC, Bayliss DA. Inhibition of a background potassium channel by Gq protein alpha-subunits.  Proc Natl Acad Sci U S A. 2006;  103 3422-3427
• 10 Lopes CM, Rohacs T, Czirjak G, Balla T, Enyedi P, Logothetis DE. PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels.  J Physiol. 2005;  564 117-129
• 11 Veale EL, Kennard LE, Sutton GL, MacKenzie G, Sandu C, Mathie A. G(alpha)q-mediated regulation of TASK3 two-pore domain potassium channels: the role of protein kinase C.  Mol Pharmacol. 2007;  71 1666-1675
• 12 Nogueira E, Xing Y, Morris C, Rainey WE. Role of angiotensin II-induced rapid response genes in the regulation of enzymes needed for aldosterone synthesis.  J Mol Endocrinol. 2009;  42 319-330
• 13 Lymperopoulos A, Rengo G, Zincarelli C, Kim J, Soltys S, Koch WJ. An adrenal beta-arrestin 1-mediated signaling pathway underlies angiotensin II-induced aldosterone production in vitro and in vivo.  Proc Natl Acad Sci U S A. 2009;  106 5825-5830
• 14 Born-Frontsberg E, Reincke M, Beuschlein F, Quinkler M. Tumor size of Conn's adenoma and comorbidities.  Horm Metab Res. 2009;  41 785-788
• 15 Young WF. Primary aldosteronism: renaissance of a syndrome.  Clin Endocrinol (Oxf). 2007;  66 607-618
• 16 Zajicek G, Ariel I, Arber N. The streaming adrenal cortex: direct evidence of centripetal migration of adrenocytes by estimation of cell turnover rate.  J Endocrinol. 1986;  111 477-482
• 17 Kim AC, Hammer GD. Adrenocortical cells with stem/progenitor cell properties: recent advances.  Mol Cell Endocrinol. 2007;  265–266 10-16
• 18 Mesiano S, Jaffe RB. Developmental and functional biology of the primate fetal adrenal cortex.  Endocr Rev. 1997;  18 378-403
• 19 Plaster NM, Tawil R, Tristani-Firouzi M, Canun S, Bendahhou S, Tsunoda A, Donaldson MR, Iannaccone ST, Brunt E, Barohn R, Clark J, Deymeer F, George AL, Fish FA, Hahn A, Nitu A, Ozdemir C, Serdaroglu P, Subramony SH, Wolfe G, Fu YH, Ptacek LJ. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome.  Cell. 2001;  105 511-519
• 20 Mu D, Chen L, Zhang X, See LH, Koch CM, Yen C, Tong JJ, Spiegel L, Nguyen KC, Servoss A, Peng Y, Pei L, Marks JR, Lowe S, Hoey T, Jan LY, McCombie WR, Wigler MH, Powers S. Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene.  Cancer Cell. 2003;  3 297-302
• 21 Pei L, Wiser O, Slavin A, Mu D, Powers S, Jan LY, Hoey T. Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function.  Proc Natl Acad Sci U S A. 2003;  100 7803-7807
• 22 Kunzelmann K. Ion channels and cancer.  J Membr Biol. 2005;  205 159-173
• 23 Bayliss DA, Barrett PQ. Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact.  Trends Pharmacol Sci. 2008;  29 566-575
• 24 Czirjak G, Enyedi P. TASK-3 dominates the background potassium conductance in rat adrenal glomerulosa cells.  Mol Endocrinol. 2002;  16 621-629
• 25 Czirjak G, Fischer T, Spat A, Lesage F, Enyedi P. TASK (TWIK-related acid-sensitive K+ channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II.  Mol Endocrinol. 2000;  14 863-874
• 26 Heitzmann D, Derand R, Jungbauer S, Bandulik S, Sterner C, Schweda F, El Wakil A, Lalli E, Guy N, Mengual R, Reichold M, Tegtmeier I, Bendahhou S, Gomez-Sanchez CE, Aller MI, Wisden W, Weber A, Lesage F, Warth R, Barhanin J. Invalidation of TASK1 potassium channels disrupts adrenal gland zonation and mineralocorticoid homeostasis.  EMBO J. 2008;  27 179-187
• 27 Davies LA, Hu C, Guagliardo NA, Sen N, Chen X, Talley EM, Carey RM, Bayliss DA, Barrett PQ. TASK channel deletion in mice causes primary hyperaldosteronism.  Proc Natl Acad Sci U S A. 2008;  105 2203-2208
• 28 Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J. TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure.  EMBO J. 1996;  15 1004-1011
• 29 Lesage F, Lazdunski M. Molecular and functional properties of two-pore-domain potassium channels.  Am J Physiol Renal Physiol. 2000;  279 F793-F801
• 30 Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M. TASK, a human background K+ channel to sense external pH variations near physiological pH.  EMBO J. 1997;  16 5464-5471
• 31 Brauneis U, Vassilev PM, Quinn SJ, Williams GH, Tillotson DL. ANG II blocks potassium currents in zona glomerulosa cells from rat, bovine, and human adrenals.  Am J Physiol. 1991;  260 E772-E779
• 32 Payet MD, Benabderrazik M, Gallo-Payet N. Excitation-secretion coupling: ionic currents in glomerulosa cells: effects of adrenocorticotropin and K+ channel blockers.  Endocrinology. 1987;  121 875-882
• 33 Lotshaw DP. Characterization of angiotensin II-regulated K+ conductance in rat adrenal glomerulosa cells.  J Membr Biol. 1997;  156 261-277
• 34 Payet MD, Durroux T, Bilodeau L, Guillon G, Gallo-Payet N. Characterization of K+ and Ca2+ ionic currents in glomerulosa cells from human adrenal glands.  Endocrinology. 1994;  134 2589-2598
• 35 Patel AJ, Honore E. Properties and modulation of mammalian 2P domain K+ channels.  Trends Neurosci. 2001;  24 339-346
• 36 Enyeart JJ, Danthi SJ, Liu H, Enyeart JA. Angiotensin II inhibits bTREK-1 K+ channels in adrenocortical cells by separate Ca2+- and ATP hydrolysis-dependent mechanisms.  J Biol Chem. 2005;  280 30814-30828
• 37 Enyeart JA, Danthi SJ, Enyeart JJ. TREK-1 K+ channels couple angiotensin II receptors to membrane depolarization and aldosterone secretion in bovine adrenal glomerulosa cells.  Am J Physiol Endocrinol Metab. 2004;  287 E1154-E1165
• 38 Enyeart JJ, Xu L, Danthi S, Enyeart JA. An ACTH- and ATP-regulated background K+ channel in adrenocortical cells is TREK-1.  J Biol Chem. 2002;  277 49186-49199
• 39 Liu H, Enyeart JA, Enyeart JJ. ACTH inhibits bTREK-1 K+ channels through multiple cAMP-dependent signaling pathways.  J Gen Physiol. 2008;  132 279-294
• 40 Wada A, Ohnishi T, Nonaka Y, Okamoto M, Yamano T. Synthesis of aldosterone by a reconstituted system of cytochrome P-45011 beta from bovine adrenocortical mitochondria.  J Biochem. 1985;  98 245-256
• 41 Lisurek M, Bernhardt R. Modulation of aldosterone and cortisol synthesis on the molecular level.  Mol Cell Endocrinol. 2004;  215 149-159
• 42 Brenner T, O'Shaughnessy KM. Both TASK-3 and TREK-1 two-pore loop K channels are expressed in H295R cells and modulate their membrane potential and aldosterone secretion.  Am J Physiol Endocrinol Metab. 2008;  295 E1480-E1486
• 43 Bayliss DA, Sirois JE, Talley EM. The TASK family: two-pore domain background K+ channels.  Mol Interv. 2003;  3 205-219
• 44 Decher N, Maier M, Dittrich W, Gassenhuber J, Bruggemann A, Busch AE, Steinmeyer K. Characterization of TASK-4, a novel member of the pH-sensitive, two-pore domain potassium channel family.  FEBS Lett. 2001;  492 84-89
• 45 Kim D, Gnatenco C. TASK-5, a new member of the tandem-pore K(+) channel family.  Biochem Biophys Res Commun. 2001;  284 923-930
• 46 Lotshaw DP. Biophysical and pharmacological characteristics of native two-pore domain TASK channels in rat adrenal glomerulosa cells.  J Membr Biol. 2006;  210 51-70
• 47 Radke KJ, Taylor RE, Schneider EG. Effect of hydrogen ion concentration on aldosterone secretion by isolated perfused canine adrenal glands.  J Endocrinol. 1986;  110 293-301
• 48 Czirjak G, Enyedi P. Formation of functional heterodimers between the TASK-1 and TASK-3 two-pore domain potassium channel subunits.  J Biol Chem. 2002;  277 5426-5432
• 49 Clarke CE, Veale EL, Green PJ, Meadows HJ, Mathie A. Selective block of the human 2-P domain potassium channel, TASK-3, and the native leak potassium current, IKSO, by zinc.  J Physiol. 2004;  560 51-62
• 50 Maingret F, Patel AJ, Lazdunski M, Honore E. The endocannabinoid anandamide is a direct and selective blocker of the background K(+) channel TASK-1.  EMBO J. 2001;  20 47-54
• 51 Lesage F, Reyes R, Fink M, Duprat F, Guillemare E, Lazdunski M. Dimerization of TWIK-1 K+ channel subunits via a disulfide bridge.  EMBO J. 1996;  15 6400-6407
• 52 Kang D, Han J, Talley EM, Bayliss DA, Kim D. Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells.  J Physiol. 2004;  554 64-77
• 53 Linden AM, Aller MI, Leppa E, Vekovischeva O, Aitta-Aho T, Veale EL, Mathie A, Rosenberg P, Wisden W, Korpi ER. The in vivo contributions of TASK-1-containing channels to the actions of inhalation anesthetics, the alpha(2) adrenergic sedative dexmedetomidine, and cannabinoid agonists.  J Pharmacol Exp Ther. 2006;  317 615-626
• 54 Meuth SG, Aller MI, Munsch T, Schuhmacher T, Seidenbecher T, Meuth P, Kleinschnitz C, Pape HC, Wiendl H, Wisden W, Budde T. The contribution of TWIK-related acid-sensitive K+-containing channels to the function of dorsal lateral geniculate thalamocortical relay neurons.  Mol Pharmacol. 2006;  69 1468-1476
• 55 Aller MI, Veale EL, Linden AM, Sandu C, Schwaninger M, Evans LJ, Korpi ER, Mathie A, Wisden W, Brickley SG. Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in cerebellar granule neurons.  J Neurosci. 2005;  25 11455-11467
• 56 Linden AM, Aller MI, Leppa E, Rosenberg PH, Wisden W, Korpi ER. K+ channel TASK-1 knockout mice show enhanced sensitivities to ataxic and hypnotic effects of GABA(A) receptor ligands.  J Pharmacol Exp Ther. 2008;  327 277-286
• 57 Trapp S, Aller MI, Wisden W, Gourine AV. A role for TASK-1 (KCNK3) channels in the chemosensory control of breathing.  J Neurosci. 2008;  28 8844-8850
• 58 Romero DG, Yanes LL, de Rodriguez AF, Plonczynski MW, Welsh BL, Reckelhoff JF, Gomez-Sanchez EP, Gomez-Sanchez CE. Disabled-2 is expressed in adrenal zona glomerulosa and is involved in aldosterone secretion.  Endocrinology. 2007;  148 2644-2652
• 59 Gummow BM, Scheys JO, Cancelli VR, Hammer GD. Reciprocal regulation of a glucocorticoid receptor-steroidogenic factor-1 transcription complex on the Dax-1 promoter by glucocorticoids and adrenocorticotropic hormone in the adrenal cortex.  Mol Endocrinol. 2006;  20 2711-2723
• 60 Ashmole I, Goodwin PA, Stanfield PR. TASK-5, a novel member of the tandem pore K+ channel family.  Pflugers Arch. 2001;  442 828-833
• 61 Karschin C, Wischmeyer E, Preisig-Muller R, Rajan S, Derst C, Grzeschik KH, Daut J, Karschin A. Expression pattern in brain of TASK-1, TASK-3, and a tandem pore domain K(+) channel subunit, TASK-5, associated with the central auditory nervous system.  Mol Cell Neurosci. 2001;  18 632-648
• 62 Jespersen T, Grunnet M, Olesen SP. The KCNQ1 potassium channel: from gene to physiological function.  Physiology (Bethesda). 2005;  20 408-416
• 63 Arrighi I, Bloch-Faure M, Grahammer F, Bleich M, Warth R, Mengual R, Drici MD, Barhanin J, Meneton P. Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome.  Proc Natl Acad Sci U S A. 2001;  98 8792-8797
• 64 Vallon V, Grahammer F, Volkl H, Sandu CD, Richter K, Rexhepaj R, Gerlach U, Rong Q, Pfeifer K, Lang F. KCNQ1-dependent transport in renal and gastrointestinal epithelia.  Proc Natl Acad Sci U S A. 2005;  102 17864-17869
• 65 Sarzani R, Pietrucci F, Francioni M, Salvi F, Letizia C, D'Erasmo E, Dessi FP, Rappelli A. Expression of potassium channel isoforms mRNA in normal human adrenals and aldosterone-secreting adenomas.  J Endocrinol Invest. 2006;  29 147-153
• 66 Abbott GW, Goldstein SA. Potassium channel subunits encoded by the KCNE gene family: physiology and pathophysiology of the MinK-related peptides (MiRPs).  Mol Interv. 2001;  1 95-107
• 67 Vallon V, Grahammer F, Richter K, Bleich M, Lang F, Barhanin J, Volkl H, Warth R. Role of KCNE1-dependent K+ fluxes in mouse proximal tubule.  J Am Soc Nephrol. 2001;  12 2003-2011
• 68 Sausbier M, Arntz C, Bucurenciu I, Zhao H, Zhou XB, Sausbier U, Feil S, Kamm S, Essin K, Sailer CA, Abdullah U, Krippeit-Drews P, Feil R, Hofmann F, Knaus HG, Kenyon C, Shipston MJ, Storm JF, Neuhuber W, Korth M, Schubert R, Gollasch M, Ruth P. Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice.  Circulation. 2005;  112 60-68
• 69 Grimm PR, Irsik DL, Settles DC, Holtzclaw JD, Sansom SC. Hypertension of Kcnmb1-/- is linked to deficient K secretion and aldosteronism.  Proc Natl Acad Sci U S A. 2009;  106 11800-11805
• 70 Knaus HG, Garcia-Calvo M, Kaczorowski GJ, Garcia ML. Subunit composition of the high conductance calcium-activated potassium channel from smooth muscle, a representative of the mSlo and slowpoke family of potassium channels.  J Biol Chem. 1994;  269 3921-3924
• 71 Meera P, Wallner M, Song M, Toro L. Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus.  Proc Natl Acad Sci U S A. 1997;  94 14066-14071
• 72 Sorensen MV, Matos JE, Sausbier M, Sausbier U, Ruth P, Praetorius HA, Leipziger J. Aldosterone increases KCa1.1 (BK) channel-mediated colonic K+ secretion.  J Physiol. 2008;  586 4251-4264
• 73 Lifton RP, Dluhy RG, Powers M, Rich GM, Gutkin M, Fallo F, Gill JR, Feld L, Ganguly A, Laidlaw JC. Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase.  Nat Genet. 1992;  2 66-74
• 74 Gordon RD, Stowasser M, Klemm SA, Tunny TJ. Primary aldosteronism--some genetic, morphological, and biochemical aspects of subtypes.  Steroids. 1995;  60 35-41
• 75 Mulatero P, Veglio F, Pilon C, Rabbia F, Zocchi C, Limone P, Boscaro M, Sonino N, Fallo F. Diagnosis of glucocorticoid-remediable aldosteronism in primary aldosteronism: aldosterone response to dexamethasone and long polymerase chain reaction for chimeric gene.  J Clin Endocrinol Metab. 1998;  83 2573-2575
• 76 Fardella CE, Pinto M, Mosso L, Gomez-Sanchez C, Jalil J, Montero J. Genetic study of patients with dexamethasone-suppressible aldosteronism without the chimeric CYP11B1/CYP11B2 gene.  J Clin Endocrinol Metab. 2001;  86 4805-4807
• 77 Wotus C, Levay-Young BK, Rogers LM, Gomez-Sanchez CE, Engeland WC. Development of adrenal zonation in fetal rats defined by expression of aldosterone synthase and 11beta-hydroxylase.  Endocrinology. 1998;  139 4397-4403
• 78 Enyeart JA, Danthi S, Enyeart JJ. Corticotropin induces the expression of TREK-1 mRNA and K+ current in adrenocortical cells.  Mol Pharmacol. 2003;  64 132-142
• 79 Kanazirska MV, Vassilev PM, Quinn SJ, Tillotson DL, Williams GH. Single K+ channels in adrenal zona glomerulosa cells. II. Inhibition by angiotensin II.  Am J Physiol. 1992;  263 E760-E765
• 80 Vassilev PM, Kanazirska MV, Quinn SJ, Tillotson DL, Williams GH. K+ channels in adrenal zona glomerulosa cells. I. Characterization of distinct channel types.  Am J Physiol. 1992;  263 E752-E759

Correspondence