Advertisement

Electrophysiological Effects of Small Conductance Ca\(^{2+}\)-Activated K\(^+\) Channels in Atrial Myocytes

  • Angelina Peñaranda
  • Inma R. Cantalapiedra
  • Enrique Alvarez-Lacalle
  • Blas EchebarriaEmail author
Chapter
  • 523 Downloads
Part of the SEMA SIMAI Springer Series book series (SEMA SIMAI, volume 20)

Abstract

Atrial fibrillation (AF), a cardiac arrhythmia characterized by an abnormal heart rythm originated in the atria, is one of the most prevalent cardiac diseases. Although it may have diverse causes, genetic screening has shown that a percentage of pacients suffering of AF present a genetic variant related to disregulation of calcium-activated potassium (SK) channels. In this paper we review the main characteristics of these channels and use several mathematical models of human atrial cardiomyocytes to study their influence in the form of the atrial action potential. We show that an overexpression of SK channels results in decreased action potential duration and, under some circumstances, it may give rise to alternans, suggesting a pro-arrhythmic role of this current. This effect becomes more important at higher pacing rates. Nevertheless, we also find it to protect against spontaneous calcium release induced afterdepolarizations, acting in this case as an antiarrhythmic factor.

Notes

Acknowledgements

We thank L. Hove-Madsen for fruitful discussions. The authors acknowledge financial support from Fundació La Marató de TV3 and from the Spanish Ministerio de Economía y Competitividad (MINECO) under grant numbers SAF2014-58286-C2-2-R, SAF2017-88019-C3-2-R and FIS2015-66503-C3-2P. IRC also acknowledges financial support from the Generalitat of Catalonia under Project 2009SGR878.

References

  1. 1.
    Adelman, J.P., Maylie, J., Sah, P.: Small-conductance Ca2+-activated K+ channels: form and function. Annu. Rev. Physiol. 74, 245–269 (2012)CrossRefGoogle Scholar
  2. 2.
    Berkefeld, H., Fakler, B., Schulte, U.: Ca2+-activated K+ channels: from protein complexes to function. Physiol. Rev. 90(4), 1437–1459 (2010)CrossRefGoogle Scholar
  3. 3.
    Blatz, A.L., Magleby, K.L.: Single apamin-blocked ca-activated K+ channels of small conductance in cultured rat skeletal muscle. Nature 323(1), 718–720 (1986)CrossRefGoogle Scholar
  4. 4.
    Carignani, C., Roncarati, R., Rimini, R., Terstappen, G.C.: Pharmacological and molecular characterisation of SK3 channels in the TE671 human medulloblastoma cell line. Brain Res. 939, 11–18 (2002)CrossRefGoogle Scholar
  5. 5.
    Cha, C.Y., Nakamura, Y., Himeno, Y., Wang, J., Fujimoto, S., Inagaki, N., Earm, Y.E., Noma, A.: Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic \(\beta \) cells: a simulation study. J. Gen. Physiol. 138(1), 21–37 (2011)CrossRefGoogle Scholar
  6. 6.
    Chay, T.R.: Effects of extracellular calcium on electrical bursting and intracellular and luminal calcium oscillations in insulin secreting pancreatic beta-cells. Biophys. J. 73(3), 1673 (1997)CrossRefGoogle Scholar
  7. 7.
    Chen, W.-T., Chen, Y.-C., Lu, Y.-Y., Kao, Y.-H., Huang, J.-H., Lin, Y.-K., Chen, S.-A., Chen, Y.-J.: Apamin modulates electrophysiological characteristics of the pulmonary vein and the sinoatrial node. Eur. J. Clin. Investig. 43(9), 957–963 (2013)CrossRefGoogle Scholar
  8. 8.
    Chua, S.-K., Chang, P.-C., Maruyama, M., Turker, I., Shinohara, T., Shen, M.J., Chen, Z., Shen, C., Rubart-von der Lohe, M., Lopshire, J.C., et al.: Small-conductance calcium-activated potassium channel and recurrent ventricular fibrillation in failing rabbit ventricles. Circ. Res. 108(8), 971–979 (2011)CrossRefGoogle Scholar
  9. 9.
    Commons, W.: File:sk channel.jpg—wikimedia commons, the free media repository (2018). Accessed 21 Jan 2019Google Scholar
  10. 10.
    Courtemanche, M., Ramirez, R.J., Nattel, S.: Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model. Am. J. Physiol.-Hear. Circ. Physiol. 275(1), H301–H321 (1998)CrossRefGoogle Scholar
  11. 11.
    Destexhe, A., Contreras, D., Sejnowski, T.J., Steriade, M.: A model of spindle rhythmicity in the isolated thalamic reticular nucleus. J. Neurophysiol. 72(2), 803–818 (1994)CrossRefGoogle Scholar
  12. 12.
    Diness, J.G., Skibsbye, L., Jespersen, T., Bartels, E.D., Sørensen, U.S., Hansen, R.S., Grunnet, M.: Effects on atrial fibrillation in aged hypertensive rats by Ca2+-activated K+ channel inhibition. Hypertension 57(6), 1129–1135 (2011)CrossRefGoogle Scholar
  13. 13.
    Diness, J.G., Sørensen, U.S., Nissen, J.D., Al-Shahib, B., Jespersen, T., Grunnet, M., Hansen, R.S.: Inhibition of small-conductance Ca2+-activated K+ channels terminates and protects against atrial fibrillation. Circulation: Arrhythmia Electrophysiol. 3(4), 380–390 (2010)Google Scholar
  14. 14.
    Ellinor, P.T., Lunetta, K.L., Glazer, N.L., Pfeufer, A., Alonso, A., Chung, M.K., Sinner, M.F., De Bakker, P.I., Mueller, M., Lubitz, S.A., et al.: Common variants in KCNN3 are associated with lone atrial fibrillation. Nat. Genet. 42(3), 240–244 (2010)CrossRefGoogle Scholar
  15. 15.
    Engel, J., Schultens, H.A., Schild, D.: Small conductance potassium channels cause an activity-dependent spike frequency adaptation and make the transfer function of neurons logarithmic. Biophys. J. 76(3), 1310–1319 (1999)CrossRefGoogle Scholar
  16. 16.
    Fridlyand, L.E., Jacobson, D., Kuznetsov, A., Philipson, L.H.: A model of action potentials and fast Ca2+ dynamics in pancreatic \(\beta \)-cells. Biophys. J. 96(8), 3126–3139 (2009)CrossRefGoogle Scholar
  17. 17.
    Goforth, P., Bertram, R., Khan, F., Zhang, M., Sherman, A., Satin, L.: Calcium-activated k+ channels of mouse \(\beta \)-cells are controlled by both store and cytoplasmic ca2+ experimental and theoretical studies. J. Gen. Physiol. 120(3), 307–322 (2002)CrossRefGoogle Scholar
  18. 18.
    Grandi, E., Pandit, S.V., Voigt, N., Workman, A.J., Dobrev, D., Jalife, J., Bers, D.M.: Human atrial action potential and Ca2+ model. Circ. Res. 109, 1055–1066 (2011).  https://doi.org/10.1161/CIRCRESAHA.111.253955CrossRefGoogle Scholar
  19. 19.
    Hille, B., et al.: Lon Channels Of Excitable Membranes, vol. 507. Sinauer Sunderland, MA (2001)Google Scholar
  20. 20.
    Hirschberg, B., Maylie, J., Adelman, J.P., Marrion, N.V.: Gating of recombinant small-conductance ca-activated K+ channels by calcium. J. Gen. Physiol. 111(4), 565–581 (1998)CrossRefGoogle Scholar
  21. 21.
    Hsueh, C.-H., Chang, P.-C., Hsieh, Y.-C., Reher, T., Chen, P.-S., Lin, S.-F.: Proarrhythmic effect of blocking the small conductance calcium activated potassium channel in isolated canine left atrium. Heart Rhythm 10(6), 891–898 (2013)CrossRefGoogle Scholar
  22. 22.
    Kennedy, M., Bers, D.M., Chiamvimonvat, N., Sato, D.: Dynamical effects of calcium-sensitive potassium currents on voltage and calcium alternans. J. Physiol. (2016)Google Scholar
  23. 23.
    Kohler, M., Hirschberg, B., Bond, C., Kinzie, J.M., et al.: Small-conductance, calcium-activated potassium channels from mammalian brain. Science 273(5282), 1709 (1996)CrossRefGoogle Scholar
  24. 24.
    Leinders, T., Vijverberg, H.: Ca2+ dependence of small Ca2+-activated K+ channels in cultured N1E-115 mouse neuroblastoma cells. Pflügers Arch. 422(3), 223–232 (1992)CrossRefGoogle Scholar
  25. 25.
    Li, N., Timofeyev, V., Tuteja, D., Xu, D., Lu, L., Zhang, Q., Zhang, Z., Singapuri, A., Albert, T.R., Rajagopal, A.V., et al.: Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation. J. Physiol. 587(5), 1087–1100 (2009)CrossRefGoogle Scholar
  26. 26.
    Ling, T.-Y., Wang, X.-L., Chai, Q., Lau, T.-W., Koestler, C.M., Park, S.J., Daly, R.C., Greason, K.L., Jen, J., Wu, L.-Q., et al.: Regulation of the SK3 channel by microRNA-499—potential role in atrial fibrillation. Heart Rhythm 10(7), 1001–1009 (2013)CrossRefGoogle Scholar
  27. 27.
    Lu, L., Zhang, Q., Timofeyev, V., Zhang, Z., Young, J.N., Shin, H.-S., Knowlton, A.A., Chiamvimonvat, N.: Molecular coupling of a Ca2+-activated K+ channel to l-type Ca2+ channels via \(\alpha \)-actinin2. Circ. Res. 100(1), 112–120 (2007)CrossRefGoogle Scholar
  28. 28.
    Lugo, C.A., Cantalapiedra, I.R., Peñaranda, A., Hove-Madsen, L., Echebarria, B.: Are SR Ca content fluctuations or SR refractoriness the key to atrial cardiac alternans?: insights from a human atrial model. Am. J. Physiol.-Heart Circ. Physiol. 306(11), H1540–H1552 (2014).  https://doi.org/10.1152/ajpheart.00515.2013CrossRefGoogle Scholar
  29. 29.
    Mears, D., Sheppard Jr., N., Atwater, I., Rojas, E., Bertram, R., Sherman, A.: Evidence that calcium release-activated current mediates the biphasic electrical activity of mouse pancreatic \(\beta \)-cells. J. Membr. Biol. 155(1), 47–59 (1997)CrossRefGoogle Scholar
  30. 30.
    Mu, Y.-H., Zhao, W.-C., Duan, P., Chen, Y., Wang, Q., Tu, H.-Y., Zhang, Q., et al.: RyR2 modulates a Ca2+-activated K+ current in mouse cardiac myocytes. PloS one 9(4), e94905 (2014)CrossRefGoogle Scholar
  31. 31.
    Nattel, S., Qi, X.Y.: Calcium-dependent potassium channels in the heart: clarity and confusion. Cardiovasc. Res. 101(2), 185–186 (2014).  https://doi.org/10.1093/cvr/cvt340CrossRefGoogle Scholar
  32. 32.
    Nygren, A., Fiset, C., Firek, L., Clark, J., Lindblad, D., Clark, R., Giles, W.: Mathematical model of an adult human atrial cell. Cardiovasc. Res. 82(1), 63–81 (1998)Google Scholar
  33. 33.
    Olesen, M.S., Jabbari, J., Holst, A.G., Nielsen, J.B., Steinbrüchel, D.A., Jespersen, T., Haunsø, S., Svendsen, J.H.: Screening of KCNN3 in patients with early-onset lone atrial fibrillation. Europace 13(7), 963–967 (2011)CrossRefGoogle Scholar
  34. 34.
    Özgen, N., Dun, W., Sosunov, E.A., Anyukhovsky, E.P., Hirose, M., Duffy, H.S., Boyden, P.A., Rosen, M.R.: Early electrical remodeling in rabbit pulmonary vein results from trafficking of intracellular SK2 channels to membrane sites. Cardiovasc. Res. 75(4), 758–769 (2007)CrossRefGoogle Scholar
  35. 35.
    Qi, X.-Y., Diness, J.G., Brundel, B.J., Zhou, X.-B., Naud, P., Wu, C.-T., Huang, H., Harada, M., Aflaki, M., Dobrev, D., et al.: Role of small-conductance calcium-activated potassium channels in atrial electrophysiology and fibrillation in the dog. Circulation 129(4), 430–440 (2014)CrossRefGoogle Scholar
  36. 36.
    Rafizadeh, S., Zhang, Z., Woltz, R.L., Kim, H.J., Myers, R.E., Lu, L., Tuteja, D., Singapuri, A., Bigdeli, A.A.Z., Harchache, S.B., et al.: Functional interaction with filamin a and intracellular Ca2+ enhance the surface membrane expression of a small-conductance Ca2+-activated K+ (SK2) channel. Proc. Natl. Acad. Sci. 111(27), 9989–9994 (2014)CrossRefGoogle Scholar
  37. 37.
    Skibsbye, L.: Antiarrhythmic principle of SK channel inhibition in atrial fibrillation. Channels 57, 672–681 (2011)Google Scholar
  38. 38.
    Skibsbye, L., Diness, J.G., Sørensen, U.S., Hansen, R.S., Grunnet, M.: The duration of pacing-induced atrial fibrillation is reduced in vivo by inhibition of small conductance Ca2+-activated K+ channels. J. Cardiovasc. Pharmacol. 57(6), 672–681 (2011)CrossRefGoogle Scholar
  39. 39.
    Skibsbye, L., Poulet, C., Diness, J.G., Bentzen, B.H., Yuan, L., Kappert, U., Matschke, K., Wettwer, E., Ravens, U., Grunnet, M., et al.: Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria. Cardiovasc. Res. 103(1), 156–167 (2014)CrossRefGoogle Scholar
  40. 40.
    Stocker, M.: Ca2+-activated K+ channels: molecular determinants and function of the SK family. Nat. Rev. Neurosci. 5(10), 758–770 (2004)CrossRefGoogle Scholar
  41. 41.
    Terentyev, D., Rochira, J.A., Terentyeva, R., Roder, K., Koren, G., Li, W.: Sarcoplasmic reticulum Ca2+ release is both necessary and sufficient for SK channel activation in ventricular myocytes. Am. J. Physiol.-Heart Circ. Physiol. 306(5), H738–H746 (2014)CrossRefGoogle Scholar
  42. 42.
    Tucker, T.R., Fettiplace, R.: Monitoring calcium in turtle hair cells with a calcium-activated potassium channel. J. Physiol. 494(Pt 3), 613 (1996)CrossRefGoogle Scholar
  43. 43.
    Tuteja, D., Xu, D., Timofeyev, V., Lu, L., Sharma, D., Zhang, Z., Xu, Y., Nie, L., Vázquez, A.E., Young, J.N., et al.: Differential expression of small-conductance Ca2+-activated K+ channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes. Am. J. Physiol.-Heart Circ. Physiol. 289(6), H2714–H2723 (2005)CrossRefGoogle Scholar
  44. 44.
    Vergara, C., Latorre, R., Marrion, N.V., Adelman, J.P.: Calcium-activated potassium channels. Curr. Opin. Neurobiol. 8(3), 321–329 (1998)CrossRefGoogle Scholar
  45. 45.
    Wang, W., Watanabe, M., Nakamura, T., Kudo, Y., Ochi, R.: Properties and expression of Ca2+-activated K+ channels in H9c2 cells derived from rat ventricle. Am. J. Physiol.-Heart Circ. Physiol. 276(5), H1559–H1566 (1999)CrossRefGoogle Scholar
  46. 46.
    Xia, X.-M., Fakler, B., Rivard, A., Wayman, G., Johnson-Pais, T., Keen, J., Ishii, T., Hirschberg, B., Bond, C., Lutsenko, S., et al.: Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature 395(6701), 503–507 (1998)CrossRefGoogle Scholar
  47. 47.
    Xu, Y., Tuteja, D., Zhang, Z., Xu, D., Zhang, Y., Rodriguez, J., Nie, L., Tuxson, H.R., Young, J.N., Glatter, K.A., et al.: Molecular identification and functional roles of a Ca2+-activated K+ channel in human and mouse hearts. J. Biol. Chem. 278(49), 49085–49094 (2003)CrossRefGoogle Scholar
  48. 48.
    Yu, T., Deng, C., Wu, R., Guo, H., Zheng, S., Yu, X., Shan, Z., Kuang, S., Lin, Q.: Decreased expression of small-conductance Ca2+-activated K+ channels SK1 and SK2 in human chronic atrial fibrillation. Life Sci. 90(5), 219–227 (2012)CrossRefGoogle Scholar
  49. 49.
    Zhang, L., McBain, C.J.: Potassium conductances underlying repolarization and after-hyperpolarization in rat CA1 hippocampal interneurones. J. Physiol. 488(Pt 3), 661 (1995)CrossRefGoogle Scholar
  50. 50.
    Zhang, X.-D., Lieu, D.K., Chiamvimonvat, N.: Small-conductance Ca2+-activated K+ channels and cardiac arrhythmias. Heart Rhythm 12(8), 1845–1851 (2015)CrossRefGoogle Scholar
  51. 51.
    Zhang, X.-D., Timofeyev, V., Li, N., Myers, R.E., Zhang, D., Singapuri, A., Lau, V.C., Bond, C.T., Adelman, J., Lieu, D.K., et al.: Critical roles of a small conductance Ca2+-activated K+ channel (SK3) in the repolarization process of atrial myocytes. Cardiovasc. Res. 101(2), 317–325 (2013).  https://doi.org/10.1093/cvr/cvt262CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Angelina Peñaranda
    • 1
  • Inma R. Cantalapiedra
    • 1
  • Enrique Alvarez-Lacalle
    • 1
  • Blas Echebarria
    • 1
    Email author
  1. 1.Departament de FísicaUniversitat Politècnica de CatalunyaBarcelonaSpain

Personalised recommendations