Ca2+-activated K+ channels of the BK-type in the mouse brain

  • Ulrike Sausbier
  • Matthias Sausbier
  • Claudia A. Sailer
  • Claudia Arntz
  • Hans-Günther Knaus
  • Winfried Neuhuber
  • Peter RuthEmail author
Original paper


An antibody against the 442 carboxy-terminal amino acids of the BK channel α-subunit detects high immunoreactivity within the telencephalon in cerebral cortices, olfactory bulb, basal ganglia and hippocampus, while lower levels are found in basal forebrain regions and amygdala. Within the diencephalon, high density was found in nuclei of the ventral and dorsal thalamus and the medial habenular nucleus, and low density in the hypothalamus. The fasciculus retroflexus and its termination in the mesencephalic interpeduncular nucleus are prominently stained. Other mesencephalic expression sites are periaquaeductal gray and raphe nuclei. In the rhombencephalon, BK channels are enriched in the cerebellar cortex and in the locus coeruleus. Strong immunoreactivity is also contained in the vestibular nuclei, but not in cranial nerves and their intramedullary course of their roots. On the cellular level, BK channels show pre- and postsynaptic localizations, i.e., in somata, dendrites, axons and synaptic terminals.


BK channel distribution Murine brain Knock out tissue validated antibody Immunofluorescence 



We thank Isolde Breuning and Clement Kabagema for excellent technical assistance, Johan Storm for critical reading the manuscript and Deutsche Forschungsgemeinschaft for financial support.


  1. Bond CT, Herson PS, Strassmaier T, Hammond R, Stackman R, Maylie J, Adelman JP (2004) Small conductance Ca2+-activated K+ channel knock-out mice reveal the identity of calcium-dependent afterhyperpolarization currents. J Neurosci 24:5301–5306CrossRefPubMedGoogle Scholar
  2. Butler A, Tsunoda S, McCobb DP, Wei A, Salkoff L (1993) mSlo, a complex mouse gene encoding “maxi” calcium-activated potassium channels. Science 261:221–224PubMedMathSciNetCrossRefGoogle Scholar
  3. Carlen PL, Gurevich N, Durand D (1982) Ethanol in low doses augments calcium-mediated mechanisms measured intracellularly in hippocampal neurons. Science 215:306–309PubMedCrossRefGoogle Scholar
  4. Carlen PL, Wilkinson DA, Wortzman G, Holgate R (1984) Partially reversible cerebral atrophy and functional improvement in recently abstinent alcoholics. Can J Neurol Sci 11(4):441–446PubMedGoogle Scholar
  5. Chavis P, Ango F, Michel JM, Bockaert J, Fagni L (1998) Modulation of big K+ channel activity by ryanodine receptors and L-type Ca2+ channels in neurons. Eur J Neurosci 10:2322–2327CrossRefPubMedGoogle Scholar
  6. Cooper EC, Jan LY (1999) Ion channel genes and human neurological disease: recent progress, prospects, and challenges. Proc Natl Acad Sci USA 96:4759–4766CrossRefPubMedGoogle Scholar
  7. Davies AG, Pierce-Shimomura JT, Kim H, VanHoven MK, Thiele TR, Bonci A, Bargmann CI, McIntire SL (2003) A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans. Cell 115:655–666CrossRefPubMedGoogle Scholar
  8. Du W, Bautista JF, Yang H, Diez-Sampedro A, You SA, Wang L, Kotagal P, Lüders HO, Shi J, Cui J, Richerson GB, Wang QK (2005) Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet 37:733–738PubMedCrossRefGoogle Scholar
  9. Edgerton JR, Reinhart PH (2003) Distinct contributions of small and large conductance Ca2+-activated K+ channels to rat Purkinje neuron function. J Physiol 548:53–69PubMedCrossRefGoogle Scholar
  10. Ermentrout B, Pascal M, Gutkin B (2001) The effects of spike frequency adaptation and negative feedback on the synchronization of neural oscillators. Neural Comput 13:1285–1310PubMedCrossRefGoogle Scholar
  11. Eunson LH, Rea R, Zuberi SM, Youroukos S, Panayiotopoulos CP, Liguori R, Avoni P, McWillian RC, Stepenson JB, Hanna MG, Kullmann DM, Spauschus A (2000) Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability. Ann Neurol 48:647–656PubMedCrossRefGoogle Scholar
  12. Faber ES, Sah P (2003) Calcium-activated potassium channels: multiple contributions to neuronal function. Neuroscientist 9:181–194PubMedCrossRefGoogle Scholar
  13. Gerlach AC, Maylie J, Adelman JP (2004) Activation kinetics of the slow afterhyperpolarization in hippocampal CA1 neurons. Pflugers Arch 448:187–196CrossRefPubMedGoogle Scholar
  14. Grunnet M, Kaufmann WA (2004) Coassembly of big conductance Ca2+-activated K+ Channels and L-type voltage-gated Ca2+ channels in rat brain. J Biol Chem 279:36445–36453CrossRefPubMedGoogle Scholar
  15. Guerrini R (2001) Idiopathic epilepsy and paroxysmal dyskinesia. Epilepsia 42:36–41CrossRefPubMedGoogle Scholar
  16. Guerrini R, Sanchez-Carpintero R, Deonna T, Santucci M, Bhatia KP, Moreno T, Parmeggiani L, Bernardina BD (2002) Early-onset absence epilepsy and paroxysmal dyskinesia. Epilepsia 43:1224–1229CrossRefPubMedGoogle Scholar
  17. Hu H, Shao LR, Chavoshy S, Gu N, Trieb M, Behrens R, Laake P, Pongs O, Knaus HG, Ottersen OP, Storm JF (2001) Presynaptic Ca2+-activated K+ channels in glutamatergic hippocampal terminals and their role in spike repolarization and regulation of transmitter release. J Neurosci 21:9585–9597PubMedGoogle Scholar
  18. Hirst WD, Abrahamsen B, Blaney FE, Calver AR, Aloj L, Price GW, Medhurst AD (2003) Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modeling. Mol Pharmacol 64:1295–1308PubMedCrossRefGoogle Scholar
  19. Isaacson JS, Murphy GJ (2001) Glutamate-mediated extrasynaptic inhibition: direct coupling of NMDA receptors to Ca2+-activated K+ channels. Neuron 31:1027–1034CrossRefPubMedGoogle Scholar
  20. Jan LY, Jan YN (1997) Ways and means for left shifts in the MaxiK channel. Proc Natl Acad Sci USA 94:13383–13385CrossRefPubMedGoogle Scholar
  21. Knaus HG, Schwarzer C, Koch RO, Eberhart A, Kaczorowski GJ, Glossmann H, Wunder F, Pongs O, Garcia ML, Sperk G (1996) Distribution of high-conductance Ca2+-activated K+ channels in rat brain: targeting to axons and nerve terminals. J Neurosci 16:955–963PubMedGoogle Scholar
  22. Larm JA, Shen PJ, Gundlach AL (2003) Differential galanin receptor-1 and galanin expression by 5-HT neurons in dorsal raphe nucleus of rat and mouse: evidence for species-dependent modulation of serotonin transmission. Eur J Neurosci 17:481–493CrossRefPubMedGoogle Scholar
  23. Levitan IB, Adams WB (1981) Cyclic AMP modulation of a specific ion channel in an identified nerve cell: possible role for protein phosphorylation. Adv Cyclic Nucleotide Res 14:647–653PubMedGoogle Scholar
  24. Marrion NV, Tavalin SJ (1998) Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons. Nature 395:900–905CrossRefPubMedGoogle Scholar
  25. Niesen CE, Baskys A, Carlen PL (1988) Reversed ethanol effects on potassium conductances in aged hippocampal dentate granule neurons. Brain Res 445:137–141CrossRefPubMedGoogle Scholar
  26. Paxinos G, Franklin KBJ (2004) The mouse brain in stereotaxic coordinates, 2nd edn. Academic, San DiegoGoogle Scholar
  27. Piggins HD, Samuels RE, Coogan AN, Cutler DJ (2001) Distribution of substance P and neurokinin-1 receptor immunoreactivity in the suprachiasmatic nuclei and intergeniculate leaflet of hamster, mouse, and rat. J Comp Neurol 438:50–65CrossRefPubMedGoogle Scholar
  28. Raffaelli G, Saviane C, Mohajerani MH, Pedarzani P, Cherubini E (2004) BK potassium channels control transmitter release at CA3–CA3 synapses in the rat hippocampus. J Physiol 557:147–157CrossRefPubMedGoogle Scholar
  29. Robitaille R, Thomas S, Charlton MP (1999) Effects of adenosine on Ca2+ entry in the nerve terminal of the frog neuromuscular junction. Can J Physiol Pharmacol 77:707–714CrossRefPubMedGoogle Scholar
  30. Rogawski MA (2000) KCNQ2/KCNQ3 K+ channels and the molecular pathogenesis of epilepsy: implications for therapy. Trends Neurosci 23:393–398CrossRefPubMedGoogle Scholar
  31. Sailer CA, Kaufmann WA, Marksteiner J, Knaus HG (2004) Comparative immunohistochemical distribution of three small-conductance Ca2+-activated potassium channel subunits, SK1, SK2, and SK3 in mouse brain. Mol Cell Neurosi 26:458–469CrossRefGoogle Scholar
  32. 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 USA 101:9474–9478CrossRefPubMedGoogle Scholar
  33. Shao LR, Halvorsrud R, Borg-Graham L, Storm JF (1999) The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells. J Physiol 521:135–146CrossRefPubMedGoogle Scholar
  34. Shipston MJ (2001) Alternative splicing of potassium channels: a dynamic switch of cellular excitability. Trends Cell Biol 11:353–358CrossRefPubMedGoogle Scholar
  35. Smith MR, Nelson AB, Du Lac S (2002) Regulation of firing response gain by calcium-dependent mechanisms in vestibular nucleus neurons. J Neurophysiol 87:2031–2042PubMedGoogle Scholar
  36. Steinlein OK, Mulley JC, Propping P, Wallace RH, Phillips HA, Sutherland GR, Scheffer IE, Berkovic SF (1995) A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet 11:201–203CrossRefPubMedGoogle Scholar
  37. Stocker M, Krause M, Pedarzani P (1999) An apamin-sensitive Ca2+-activated K+ current in hippocampal pyramidal neurons. Proc Natl Acad Sci USA 96:4662–4667CrossRefPubMedGoogle Scholar
  38. Stocker M, Pedarzani P (2000) Differential distribution of three Ca2+-activated K+ channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system. Mol Cell Neurosci 15:476–493CrossRefPubMedGoogle Scholar
  39. Storm JF (1987) Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells. J Physiol 385:733–759PubMedGoogle Scholar
  40. Storm JF (1990) Potassium currents in hippocampal pyramidal cells. Prog Brain Res 83:161–187PubMedCrossRefGoogle Scholar
  41. Sun X, Gu XQ, Haddad GG (2003) Calcium influx via L- and N-type calcium channels activates a transient large-conductance Ca2+-activated K+ current in mouse neocortical pyramidal neurons. J Neurosci 23:3639–3648PubMedGoogle Scholar
  42. Turnbull J, Lohi H, Kearney JA, Rouleau GA, Delgado-Escueta AV, Meisler MH, Cossette P, Minassian BA (2005) Sacred disease secrets revealed: the genetics of human epilepsy. Hum Mol Genet 14:2491–2500CrossRefGoogle Scholar
  43. Watanabe H, Nagata E, Kosakai A, Nakamura M, Yokoyama M, Tanaka K, Sasai H (2000) Disruption of the epilepsy KCNQ2 gene results in neural hyperexcitability. J Neurochem 75:28–33CrossRefPubMedGoogle Scholar
  44. Womack MD, Khodakhah K (2004) Dendritic control of spontaneous bursting in cerebellar Purkinje cells. J Neurosci 24:3511–3521CrossRefPubMedGoogle Scholar
  45. Womack MD, Chevez C, Khodakhah K (2004) Calcium-activated potassium channels are selectively coupled to P/Q-type calcium channels in cerebellar Purkinje neurons. J Neurosci 24:8818–8822CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Ulrike Sausbier
    • 1
  • Matthias Sausbier
    • 1
  • Claudia A. Sailer
    • 2
  • Claudia Arntz
    • 1
  • Hans-Günther Knaus
    • 2
  • Winfried Neuhuber
    • 3
  • Peter Ruth
    • 1
    Email author
  1. 1.Pharmakologie und ToxikologiePharmazeutisches Institut der Universität TübingenTübingenGermany
  2. 2.Division für Molekulare und Zelluläre PharmakologieMedizinische Universität InnsbruckInnsbruckAustria
  3. 3.Institut für Anatomie der Friedrich-Alexander-Universität Erlangen-NürnbergNürnbergGermany

Personalised recommendations