The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Modulation of Large Conductance $Ca^{2+}-activated$ $K^+4$ Channel of Skin Fibroblast (CRL-1474) by Cyclic Nucleotides

  • Yun, Ji-Hyun (Department of Physiology, College of Medicine, Chung-Ang University) ;
  • Kim, Seung-Tae (Department of Physiology, College of Medicine, Chung-Ang University) ;
  • Bang, Hyo-Weon (Department of Physiology, College of Medicine, Chung-Ang University)
  • Published : 2005.04.21
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Abstract

Potassium channels in human skin fibroblast have been studied as a possible site of Alzheimer disease pathogenesis. Fibroblasts in Alzheimer disease show alterations in signal transduction pathway such as changes in $Ca^{2+}$ homeostasis and/or $Ca^{2+}-activated$ kinases, phosphatidylinositol cascade, protein kinase C activity, cAMP levels and absence of specific $K^+$ channel. However, little is known so far about electrophysiological and pharmacological characteristics of large-conductance $Ca^{2+}$-activated $K^+$ ($BK_{Ca}$) channel in human fibroblast (CRL-1474). In the present study, we found Iberiotoxin- and TEA-sensitive outward rectifying oscillatory current with whole-cell recordings. Single channel analysis showed large conductance $K^{+}$ channels (106 pS of chord conductance at +40 mV in physiological $K^+$ gradient). The 106 pS channels were activated by membrane potential and $[Ca^{2+}]_i$, consistent with the known properties of $BK_{Ca}$ channels. $BK_{Ca}$ channels in CRL-1474 were positively regulated by adenylate cyclase activator ($10{\mu}M$ forskolin), 8-Br-cyclic AMP ($300{\mu}M$) or 8-Br-cyclic GMP ($300{\mu}M$). These results suggest that human skin fibroblasts (CR-1474) have typical $BK_{Ca}$ channel and this channel could be modulated by c-AMP and c-GMP. The electrophysiological characteristics of fibroblasts might be used as the diagnostic clues for Alzheimer disease.

Keywords

References

  1. Atkinson N, Brenner R, Chang W-M, Wilbur JL, Larimer JL, Yu J. Molecular separation of two behavioral phenotypes by a mutation affecting the promoters of a $Ca^{2+}$-activated $K^+$ channel. J Neurosci 20: 2988-2993, 2000
  2. Baron A, Frieden M, Chabaud F, Beny JL. $Ca^{2+}$-dependent nonselective cation and potassium channels activated by bradykinin in pig coronary artery endothelial cells. J Physiol (Lond) 493: 691-706, 1996 https://doi.org/10.1113/jphysiol.1996.sp021415
  3. Bielefeldt K, Jackson MB. Phosphorylation and dephosphorylation modulate a $Ca^{2+}$-activated $K^+$ channel in rat peptidergic nerve terminals. J Physiol (Lond) 475: 241-254, 1994 https://doi.org/10.1113/jphysiol.1994.sp020065
  4. Breitwieser GE. Mechanisms of $K^+$ channel Regulation. J Memb Biol 152: 1-11, 1996 https://doi.org/10.1007/s002329900080
  5. Brenner R, Yu JY, Srinivasan K, Brewer L, Larimer JL, Wilbur JL, Atkinson NS. Complementation of physiological and behavioral defects by a slowpoke $Ca^{2+}$-activated $K^+$ channel transgene. J Neurochem 75: 1310-1319, 2000 https://doi.org/10.1046/j.1471-4159.2000.751310.x
  6. Dhanakoti SN, Gao Y, Nguyen MQ, Raj JU. Involvement of pulmonary arteries to cGMP and cAMP. J Appl Physiol 88: 1637-1642, 2000 https://doi.org/10.1152/jappl.2000.88.5.1637
  7. Etcheberrigaray R, Ito E, Oka K, Tofel-Grehl B, Gibson G, Alkon DL. Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease. Proc Natl Acad Sci USA 90: 8209-8213, 1993 https://doi.org/10.1073/pnas.90.17.8209
  8. Garcia ML, Kaczorowski GJ. High conductance calcium-activated potassium channels: molecular pharmacology, purification and regulation In: Weston AH, Hamilton TC ed, Potassium Channel Modulators. Blackwell Scientific Publications, Oxford, p 76-109, 1992
  9. Gho M, Ganetzky B. Analysis of repolarization of presynaptic motor terminals in Drosophilia larvae using potassium channelblocking drugs and mutations. J Exp Biol 170: 93-111, 1992
  10. Horsburgh K, Daitoh T. Altered signal transduction in Alzheimer's disease, In: Terry RD, Katzman R, Bick KL ed, Alzheimer's Disease. Raven Press, New York, p 387-404, 1994
  11. Huang HM, Gibson GE. Altered ${\beta}-adrenergic$ receptor-stimulated cAMP formation in cultured skin fibroblasts from Alzheimer donors. J Biol Chem 268: 14616-14621, 1993
  12. Klæke DA, Wienert H, Zeuthen T, Jogensen PL. Regulation of $Ca^{2+}$-activated $K^+$ channel from rabbit distal colon epithelium by phosphorylation and dephosphorylation. J Membrane Biol 151: 11-18, 1996 https://doi.org/10.1007/s002329900053
  13. Knaus HG, Schwarzer C, Koch RO, Eberhart A, Kaczorowske GJ, Glossmann H, Wunder F, Pongs O, Garcia ML, Sperk G. Distribution of high-conductance $Ca^{2+}$-activated $K^+$ channels in rat brain:targeting to axons and nerve terminals. J Neurosci 16: 955-963, 1996
  14. Kohler R, Schongelder G, Hopp H, Distler A, Hoyer J. Stretchactivated cation channel in human umbilical vein endothelium in normal pregnancy and in preeclampsia. J Hypertens 16: 1149-1156, 1998 https://doi.org/10.1097/00004872-199816080-00011
  15. Latorre R, Oberhauser A, Labarca P, Alvarez O. Varieties of calcium-activated potassium channels. Annu Rev Physiol 51: 385-399, 1989 https://doi.org/10.1146/annurev.ph.51.030189.002125
  16. Lincoln TM, Cornwell TL, Taylor AE. cGMP-dependent protein kinase mediates the reduction of $Ca^{2+}$ by cAMP in vascular smooth muscle cells. Am J Physiol 258: C399-407, 1990 https://doi.org/10.1152/ajpcell.1990.258.3.C399
  17. Malow BA, Baker AC, Blass JP. Cultured cells as a screen for novel treatments of Alzheimer's disease. Arch Neurol 46: 1201-1203, 1989 https://doi.org/10.1001/archneur.1989.00520470057027
  18. Martinez M, Fernandez E, Frank A, Guaza C, De la Fuente M, Hernanz A. Increased cerebrospinal fluid cAMP levels in Alzheimer's disease. Brain Res 846: 265-267, 1999 https://doi.org/10.1016/S0006-8993(99)01981-2
  19. Nelson MT, Quayle JM. Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 268: C799-822, 1995 https://doi.org/10.1152/ajpcell.1995.268.4.C799
  20. Sansom SC, Stockand JD. Differential $Ca^{2+}$ sensitivities of BKCa isochannels in bovine mesenteric artery. Am J Physiol 266: C1182-1189, 1994 https://doi.org/10.1152/ajpcell.1994.266.5.C1182
  21. Wallner M, Meea P, Toro L. Calcium-activated potassium channels in muscle and brain. In: Kurachi Y, Jan LY, Lazdunski M ed, Potassium Ion Channels; Molecular Structure, Function and Diseases. Acdemic Press, San Diego, p 117-140, 1999
  22. White RE, Kryman JP, El-Mowafy A, Han G, Carrier GO. cAMP-dependent vasodilators cross-activate the cGMP dependent protein kinase to stimulate $BK_{Ca}$ channel activity in coronary artery smooth muscle. Circ Res 86: 897-905, 2000 https://doi.org/10.1161/01.RES.86.8.897