Regulation of connexin36 gap junction channels by n-alkanols and arachidonic acid

Alina Marandykina, Nicolás Palacios-Prado, Lina Rimkute, Vytenis A. Skeberdis, Feliksas F. Bukauskas

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

We examined junctional conductance (gj) and its dependence on transjunctional voltage in gap junction (GJ) channels formed of wild-type connexin36 (Cx36) or its fusion form with green fluorescent protein (Cx36-EGFP) transfected in HeLa cells or endogenously expressed in primary culture of pancreatic β-cells. Only a very small fraction (∼0.8%) of Cx36-EGFP channels assembled into junctional plaques of GJs were open under control conditions. We found that short carbon chain n-alkanols (SCCAs) increased gj, while long carbon chain n-alkanols resulted in full uncoupling; cutoff is between heptanol and octanol. The fraction of functional channels and gj increased several fold under an exposure to SCCAs, or during reduction of endogenous levels of arachidonic acid (AA) by exposure to fatty acid-free BSA or cytosolic phospholipase A2 inhibitors. Moreover, uncoupling caused by exogenously applied AA can be rescued by BSA, which binds AA and other polyunsaturated fatty acids (PUFAs), but not by BSA modified with 1,2-cyclohexanedione, which does not bind AA and other PUFAs. We propose that under control conditions, Cx36 GJ channels in HeLa transfectants and β-cells are inhibited by endogenous AA, which stabilizes a closed conformational state of the channel that leads to extremely low fraction of functional channels. In addition, SCCAs increase gj by interfering with endogenous AA-dependent inhibition, increasing open probability and the fraction of functional channels.

Original languageEnglish (US)
Pages (from-to)2087-2101
Number of pages15
JournalJournal of Physiology
Volume591
Issue number8
DOIs
StatePublished - Apr 2013

Fingerprint

Gap Junctions
Arachidonic Acid
Carbon
Unsaturated Fatty Acids
HeLa Cells
Phospholipase A2 Inhibitors
Heptanol
Octanols
Primary Cell Culture
Green Fluorescent Proteins
Nonesterified Fatty Acids
connexin 36

ASJC Scopus subject areas

  • Physiology

Cite this

Marandykina, A., Palacios-Prado, N., Rimkute, L., Skeberdis, V. A., & Bukauskas, F. F. (2013). Regulation of connexin36 gap junction channels by n-alkanols and arachidonic acid. Journal of Physiology, 591(8), 2087-2101. https://doi.org/10.1113/jphysiol.2013.250910

Regulation of connexin36 gap junction channels by n-alkanols and arachidonic acid. / Marandykina, Alina; Palacios-Prado, Nicolás; Rimkute, Lina; Skeberdis, Vytenis A.; Bukauskas, Feliksas F.

In: Journal of Physiology, Vol. 591, No. 8, 04.2013, p. 2087-2101.

Research output: Contribution to journalArticle

Marandykina, A, Palacios-Prado, N, Rimkute, L, Skeberdis, VA & Bukauskas, FF 2013, 'Regulation of connexin36 gap junction channels by n-alkanols and arachidonic acid', Journal of Physiology, vol. 591, no. 8, pp. 2087-2101. https://doi.org/10.1113/jphysiol.2013.250910
Marandykina A, Palacios-Prado N, Rimkute L, Skeberdis VA, Bukauskas FF. Regulation of connexin36 gap junction channels by n-alkanols and arachidonic acid. Journal of Physiology. 2013 Apr;591(8):2087-2101. https://doi.org/10.1113/jphysiol.2013.250910
Marandykina, Alina ; Palacios-Prado, Nicolás ; Rimkute, Lina ; Skeberdis, Vytenis A. ; Bukauskas, Feliksas F. / Regulation of connexin36 gap junction channels by n-alkanols and arachidonic acid. In: Journal of Physiology. 2013 ; Vol. 591, No. 8. pp. 2087-2101.
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