Regulation of connexin hemichannels by monovalent cations

Miduturu Srinivas, D. Paola Calderon, Jack Kronengold, Vytautas Verselis

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Opening of connexin hemichannels in the plasma membrane is highly regulated. Generally, depolarization and reduced extracellular Ca2+ promote hemichannel opening. Here we show that hemichannels formed of Cx50, a principal lens connexin, exhibit a novel form of regulation characterized by extraordinary sensitivity to extracellular monovalent cations. Replacement of extracellular Na+ with K+, while maintaining extracellular Ca2+ constant, resulted in >10-fold potentiation of Cx50 hemichannel currents, which reversed upon returning to Na+. External Cs+, Rb+, NH4+, but not Li +, choline, or TEA, exhibited a similar effect. The magnitude of potentiation of Cx50 hemichannel currents depended on the concentration of extracellular Ca2+, progressively decreasing as external Ca 2+ was reduced. The primary effect of K+ appears to be a reduction in the ability of Ca2+, as well as other divalent cations, to close Cx50 hemichannels. Cx46 hemichannels exhibited a modest increase upon substituting Na+ with K+. Analyses of reciprocal chimeric hemichannels that swap NH2- and COOH-terminal halves of Cx46 and Cx50 demonstrate that the difference in regulation by monovalent ions in these connexins resides in the NH2-terminal half. Connexin hemichannels have been implicated in physiological roles, e.g., release of ATP and NAD + and in pathological roles, e.g., cell death through loss or entry of ions and signaling molecules. Our results demonstrate a new, robust means of regulating hemichannels through a combination of extracellular monovalent and divalent cations, principally Na+, K+, and Ca 2+.

Original languageEnglish (US)
Pages (from-to)67-75
Number of pages9
JournalJournal of General Physiology
Volume127
Issue number1
DOIs
StatePublished - Jan 2006

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Monovalent Cations
Connexins
Divalent Cations
Ions
Choline
NAD
Lenses
Cell Death
Adenosine Triphosphate
Cell Membrane

ASJC Scopus subject areas

  • Physiology

Cite this

Regulation of connexin hemichannels by monovalent cations. / Srinivas, Miduturu; Calderon, D. Paola; Kronengold, Jack; Verselis, Vytautas.

In: Journal of General Physiology, Vol. 127, No. 1, 01.2006, p. 67-75.

Research output: Contribution to journalArticle

Srinivas, Miduturu ; Calderon, D. Paola ; Kronengold, Jack ; Verselis, Vytautas. / Regulation of connexin hemichannels by monovalent cations. In: Journal of General Physiology. 2006 ; Vol. 127, No. 1. pp. 67-75.
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