Cholesterol increases the open probability of cardiac KACh currents

Anna Bukiya, Catherine V. Osborn, Guruprasad Kuntamallappanavar, Peter T. Toth, Lia Baki, Gregory Kowalsky, Myung J. Oh, Alejandro Dopico, Irena Levitan, Avia Rosenhouse-Dantsker

Research output: Contribution to journalArticle

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Abstract

Abstract Cholesterol is one of the major lipid components of membranes in mammalian cells. In recent years, cholesterol has emerged as a major regulator of ion channel function. The most common effect of cholesterol on ion channels in general and on inwardly rectifying potassium (Kir) channels in particular is a decrease in activity. In contrast, we have recently shown that native G-protein gated Kir (GIRK or Kir3) channels that underlie atrial KACh currents are up-regulated by cholesterol. Here we unveil the biophysical basis of cholesterol-induced increase in KACh activity. Using planar lipid bilayers we show that cholesterol significantly enhances the channel open frequency of the Kir3.1/Kir3.4 channels, which underlie KACh currents. In contrast, our data indicate that cholesterol does not affect their unitary conductance. Furthermore, using fluorescent and TIRF microscopy as well as surface protein biotinylation, we also show that cholesterol enrichment in vitro has no effect on surface expression of GFP-tagged channels expressed in Xenopus oocytes or transfected into HEK293 cells. Together, these data demonstrate for the first time that cholesterol enhances Kir3-mediated current by increasing the channel open probability.

Original languageEnglish (US)
Article number81951
Pages (from-to)2406-2413
Number of pages8
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1848
Issue number10
DOIs
StatePublished - Aug 8 2015

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Cholesterol
Ion Channels
Inwardly Rectifying Potassium Channel
Biotinylation
Lipid bilayers
HEK293 Cells
Lipid Bilayers
Membrane Lipids
Xenopus
GTP-Binding Proteins
Oocytes
Microscopy
Potassium
Microscopic examination
Membrane Proteins
Cells
Membranes
Lipids

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Bukiya, A., Osborn, C. V., Kuntamallappanavar, G., Toth, P. T., Baki, L., Kowalsky, G., ... Rosenhouse-Dantsker, A. (2015). Cholesterol increases the open probability of cardiac KACh currents. Biochimica et Biophysica Acta - Biomembranes, 1848(10), 2406-2413. [81951]. https://doi.org/10.1016/j.bbamem.2015.07.007

Cholesterol increases the open probability of cardiac KACh currents. / Bukiya, Anna; Osborn, Catherine V.; Kuntamallappanavar, Guruprasad; Toth, Peter T.; Baki, Lia; Kowalsky, Gregory; Oh, Myung J.; Dopico, Alejandro; Levitan, Irena; Rosenhouse-Dantsker, Avia.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1848, No. 10, 81951, 08.08.2015, p. 2406-2413.

Research output: Contribution to journalArticle

Bukiya, A, Osborn, CV, Kuntamallappanavar, G, Toth, PT, Baki, L, Kowalsky, G, Oh, MJ, Dopico, A, Levitan, I & Rosenhouse-Dantsker, A 2015, 'Cholesterol increases the open probability of cardiac KACh currents', Biochimica et Biophysica Acta - Biomembranes, vol. 1848, no. 10, 81951, pp. 2406-2413. https://doi.org/10.1016/j.bbamem.2015.07.007
Bukiya A, Osborn CV, Kuntamallappanavar G, Toth PT, Baki L, Kowalsky G et al. Cholesterol increases the open probability of cardiac KACh currents. Biochimica et Biophysica Acta - Biomembranes. 2015 Aug 8;1848(10):2406-2413. 81951. https://doi.org/10.1016/j.bbamem.2015.07.007
Bukiya, Anna ; Osborn, Catherine V. ; Kuntamallappanavar, Guruprasad ; Toth, Peter T. ; Baki, Lia ; Kowalsky, Gregory ; Oh, Myung J. ; Dopico, Alejandro ; Levitan, Irena ; Rosenhouse-Dantsker, Avia. / Cholesterol increases the open probability of cardiac KACh currents. In: Biochimica et Biophysica Acta - Biomembranes. 2015 ; Vol. 1848, No. 10. pp. 2406-2413.
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AU - Kowalsky, Gregory

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