Skip to main content
SpringerLink
Log in

17β-Estradiol Upregulated Expression of α and β Subunits of Larger-Conductance Calcium-Activated K+ Channels (BK) via Estrogen Receptor β

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Large-conductance Ca2+-activated K+ channels, which were known as BK channels, were widely distributed in brain tissues and played a crucial role in neuroprotection. Previous studies found that estrogen, a steroid hormone, was able to interact with distinct K+ channels such as Kv (voltage-gated K+ channels) in various tissues. However, current knowledge about possible effects of estrogen on BK channels is rather poor. In the present study here, the investigation for the interaction of estrogen with BK channels was performed in mouse N2A cells and human SK-N-SH cells. At first, the different expression patterns of α and β subunits of BK channels in these cells were explored by conducting RT-PCR. After exposure to varying dose of 17β-estradiol (E2) for 24 h, the messenger RNA (mRNA) levels of these BK channel subunits in both N2A and SK-N-SH cells were significantly increased in a concentration-dependent way. A prolonged incubation for 48 h also potentiated the effects of E2 on β1 and β4 subunits in N2A cells as well as α and β3 subunits in SK-N-SH cells. The small interfering RNAs (siRNAs) against the ERα (siERα) or ERβ (siERβ) was induced into N2A and SK-N-SH cells by transfection and resulted in a decrease in the level of corresponding ER transcript. Furthermore, treatment with siERβ but not siERα attenuated the action of E2 on BK channel subunits, suggesting that estradiol exerted its action by binding to ERβ. Our data indicated that 17β-estradiol was able to regulate the expression of BK channel subunits via ERβ.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  • Adelman JP, Shen KZ, Kavanaugh MP, Warren RA, Wu YN, Lagrutta A, Bond CT, North RA (1992) Calcium-activated potassium channels expressed from cloned complementary DNAs. Neuron 9(2):209–216

    Article  CAS  PubMed  Google Scholar 

  • Ba F, Pang PK, Davidge ST, Benishin CG (2004) The neuroprotective effects of estrogen in SK-N-SH neuroblastoma cell cultures. Neurochem Int 44(6):401–411

    Article  CAS  PubMed  Google Scholar 

  • Backus KH, Trube G (1993) Single-channel activity in cultured cortical neurons of the rat in the presence of a toxic dose of glutamate. Eur J Neurosci 5(2):174–185

    Article  CAS  PubMed  Google Scholar 

  • Brenner R, Jegla TJ, Wickenden A, Liu Y, Aldrich RW (2000) Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4. J Biol Chem 275(9):6453–6461

    Article  CAS  PubMed  Google Scholar 

  • Chang CP, Dworetzky SI, Wang J, Goldstein ME (1997) Differential expression of the alpha and beta subunits of the large-conductance calcium-activated potassium channel: implication for channel diversity. Brain Res Mol Brain Res 45(1):33–40

    Article  CAS  PubMed  Google Scholar 

  • Cheskis BJ, Greger JG, Nagpal S, Freedman LP (2007) Signaling by estrogens. J Cell Physiol 213(3):610–617. doi:10.1002/jcp.21253

    Article  CAS  PubMed  Google Scholar 

  • Faber ES, Sah P (2003) Calcium-activated potassium channels: multiple contributions to neuronal function. Neuroscientist 9(3):181–194

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Calvo M, Knaus HG, McManus OB, Giangiacomo KM, Kaczorowski GJ, Garcia ML (1994) Purification and reconstitution of the high-conductance, calcium-activated potassium channel from tracheal smooth muscle. J Biol Chem 269(1):676–682

    CAS  PubMed  Google Scholar 

  • Green PS, Bishop J, Simpkins JW (1997) 17 alpha-estradiol exerts neuroprotective effects on SK-N-SH cells. J Neurosci 17(2):511–515

    CAS  PubMed  Google Scholar 

  • Gribkoff VK, Starrett JE Jr, Dworetzky SI (2001) Maxi-K potassium channels: form, function, and modulation of a class of endogenous regulators of intracellular calcium. Neuroscientist 7(2):166–177

    Article  CAS  PubMed  Google Scholar 

  • Kelly MJ, Levin ER (2001) Rapid actions of plasma membrane estrogen receptors. Trends Endocrinol Metab 12(4):152–156

    Article  CAS  PubMed  Google Scholar 

  • Kim N, Chung J, Kim E, Han J (2003) Changes in the Ca2 + -activated K+ channels of the coronary artery during left ventricular hypertrophy. Circ Res 93(6):541–547. doi:10.1161/01.res.0000090087.66390.f2

    Article  CAS  PubMed  Google Scholar 

  • Mendez P, Garcia-Segura LM (2006) Phosphatidylinositol 3-kinase and glycogen synthase kinase 3 regulate estrogen receptor-mediated transcription in neuronal cells. Endocrinology 147(6):3027–3039. doi:10.1210/en.2005-1224

    Article  CAS  PubMed  Google Scholar 

  • Merchenthaler I, Lane MV, Numan S, Dellovade TL (2004) Distribution of estrogen receptor alpha and beta in the mouse central nervous system: in vivo autoradiographic and immunocytochemical analyses. J Comp Neurol 473(2):270–291. doi:10.1002/cne.20128

    Article  CAS  PubMed  Google Scholar 

  • Naftolin F, Cutmann JN, Decherney AH, Sarrel PM (1990) Ovarian secretions and cardiovascular and neurological function. Raven, New York

    Google Scholar 

  • Nelson MT, Cheng H, Rubart M, Santana LF, Bonev AD, Knot HJ, Lederer WJ (1995) Relaxation of arterial smooth muscle by calcium sparks. Science 270(5236):633–637

    Article  CAS  PubMed  Google Scholar 

  • Nishimura I, Ui-Tei K, Saigo K, Ishii H, Sakuma Y, Kato M (2008) 17beta-estradiol at physiological concentrations augments Ca(2+) -activated K+ currents via estrogen receptor beta in the gonadotropin-releasing hormone neuronal cell line GT1-7. Endocrinology 149(2):774–782. doi:10.1210/en.2007-0759

    Article  CAS  PubMed  Google Scholar 

  • Noe G, Cheng YC, Dabike M, Croxatto HB (1992) Tissue uptake of human sex hormone-binding globulin and its influence on ligand kinetics in the adult female rat. Biol Reprod 47(6):970–976

    Article  CAS  PubMed  Google Scholar 

  • Petrovska S, Dejanova B, Jurisic V (2012) Estrogens: mechanisms of neuroprotective effects. J Physiol Biochem 68(3):455–460. doi:10.1007/s13105-012-0159-x

    Article  CAS  PubMed  Google Scholar 

  • Reinhart PH, Levitan IB (1995) Kinase and phosphatase activities intimately associated with a reconstituted calcium-dependent potassium channel. J Neurosci 15(6):4572–4579

    CAS  PubMed  Google Scholar 

  • Robitaille R, Charlton MP (1992) Presynaptic calcium signals and transmitter release are modulated by calcium-activated potassium channels. J Neurosci 12(1):297–305

    CAS  PubMed  Google Scholar 

  • Rothberg BS (2004) Allosteric modulation of ion channels: the case of maxi-K. Sci STKE 2004(227):pe16. doi:10.1126/stke.2272004pe16

    PubMed  Google Scholar 

  • Runnebaum B, Raube T (1987) Gynaekologische Endokrinologie. Springer, New York

    Book  Google Scholar 

  • Salzmann M, Seidel KN, Bernard R, Pruss H, Veh RW, Derst C (2010) BKbeta1 subunits contribute to BK channel diversity in rat hypothalamic neurons. Cell Mol Neurobiol 30(6):967–976. doi:10.1007/s10571-010-9527-7

    Article  CAS  PubMed  Google Scholar 

  • Sausbier M, Hu H, Arntz C, Feil S, Kamm S, Adelsberger H, Sausbier U, Sailer CA, Feil R, Hofmann F, Korth M, Shipston MJ, Knaus HG, Wolfer DP, Pedroarena CM, Storm JF, Ruth P (2004) Cerebellar ataxia and Purkinje cell dysfunction caused by Ca2 + -activated K+ channel deficiency. Proc Natl Acad Sci U S A 101(25):9474–9478. doi:10.1073/pnas.0401702101

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Seidel KN, Derst C, Salzmann M, Holtje M, Priller J, Markgraf R, Heinemann SH, Heilmann H, Skatchkov SN, Eaton MJ, Veh RW, Pruss H (2011) Expression of the voltage- and Ca2 + -dependent BK potassium channel subunits BKbeta1 and BKbeta4 in rodent astrocytes. Glia 59(6):893–902. doi:10.1002/glia.21160

    Article  PubMed  Google Scholar 

  • Shen KZ, Lagrutta A, Davies NW, Standen NB, Adelman JP, North RA (1994) Tetraethylammonium block of Slowpoke calcium-activated potassium channels expressed in Xenopus oocytes: evidence for tetrameric channel formation. Pflugers Arch 426(5):440–445

    Article  CAS  PubMed  Google Scholar 

  • Tseng-Crank J, Godinot N, Johansen TE, Ahring PK, Strobaek D, Mertz R, Foster CD, Olesen SP, Reinhart PH (1996) Cloning, expression, and distribution of a Ca(2+)-activated K+ channel beta-subunit from human brain. Proc Natl Acad Sci U S A 93(17):9200–9205

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Uebele VN, Lagrutta A, Wade T, Figueroa DJ, Liu Y, McKenna E, Austin CP, Bennett PB, Swanson R (2000) Cloning and functional expression of two families of beta-subunits of the large conductance calcium-activated K+ channel. J Biol Chem 275(30):23211–23218. doi:10.1074/jbc.M910187199

    Article  CAS  PubMed  Google Scholar 

  • Valverde MA, Rojas P, Amigo J, Cosmelli D, Orio P, Bahamonde MI, Mann GE, Vergara C, Latorre R (1999) Acute activation of Maxi-K channels (hSlo) by estradiol binding to the beta subunit. Science 285(5435):1929–1931

    Article  CAS  PubMed  Google Scholar 

  • Watson CS, Gametchu B (2003) Proteins of multiple classes may participate in nongenomic steroid actions. Exp Biol Med (Maywood) 228(11):1272–1281

    CAS  Google Scholar 

  • White WB (2003) Clinical trial experience around the globe: focus on calcium-channel blockers. Clin Cardiol 26(2 Suppl 2):II7–II11

    Article  PubMed  Google Scholar 

  • White RE, Han G, Maunz M, Dimitropoulou C, El-Mowafy AM, Barlow RS, Catravas JD, Snead C, Carrier GO, Zhu S, Yu X (2002) Endothelium-independent effect of estrogen on Ca(2+)-activated K(+) channels in human coronary artery smooth muscle cells. Cardiovasc Res 53(3):650–661

    Article  CAS  PubMed  Google Scholar 

  • Yazejian B, DiGregorio DA, Vergara JL, Poage RE, Meriney SD, Grinnell AD (1997) Direct measurements of presynaptic calcium and calcium-activated potassium currents regulating neurotransmitter release at cultured Xenopus nerve-muscle synapses. J Neurosci 17(9):2990–3001

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the grants from Basic research project of SCUN [YCZY12019].

Author information

Author notes

    Authors and Affiliations

    1. Department of Neuroscience, College of Life Sciences, South-Central University for Nationalities, 182 Minyuan Road, Wuhan, 430074, China

      Xian-Tao Li

    2. South-Central University for Nationalities, Wuhan, 430074, China

      Xiao-Yue Qiu

    Authors
    1. Xian-Tao Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Xiao-Yue Qiu
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Xian-Tao Li.

    Additional information

    Xian-Tao Li and Xiao-Yue Qiu contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Li, XT., Qiu, XY. 17β-Estradiol Upregulated Expression of α and β Subunits of Larger-Conductance Calcium-Activated K+ Channels (BK) via Estrogen Receptor β. J Mol Neurosci 56, 799–807 (2015). https://doi.org/10.1007/s12031-015-0502-0

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12031-015-0502-0

    Keywords

    Search

    Navigation