期刊
JOURNAL OF GENERAL PHYSIOLOGY
卷 127, 期 1, 页码 67-75出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1085/jgp.200509397
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资金
- NATIONAL EYE INSTITUTE [R01EY013869] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM054179] Funding Source: NIH RePORTER
- NEI NIH HHS [R01 EY013869, EY13869] Funding Source: Medline
- NIGMS NIH HHS [GM54179, R01 GM054179] Funding Source: Medline
- NINDS NIH HHS [TS-NS07439, T32 NS007439] Funding Source: Medline
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 Ca2+ 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 Ca2+.
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