TY - JOUR
T1 - Voltage gating and permeation in a gap junction hemichannel
AU - Trexler, E. Brady
AU - Bennett, Michael V.L.
AU - Bargiello, Thaddeus A.
AU - Verselis, Vytas K.
PY - 1996/6/11
Y1 - 1996/6/11
N2 - Gap junction channels are formed by members of the connexin gene family and mediate direct intercellular communication through linked hemichannels (connexons) from each of two adjacent cells. While for most connexins, the hemichannels appear to require an apposing hemichannel to open, macroscopic currents obtained from Xenopus oocytes expressing rat Cx46 suggested that some hemichannels can be readily opened by membrane depolarization [Paul, D. L., Ebihara, L., Takemoto, L. J., Swenson, K. I. and Goodenough, D. A. (1991), J. Cell Biol. 115, 1077-1089]. Here we demonstrate by single channel recording that hemichannels comprised of rat Cx46 exhibit complex voltage gating consistent with there being two distinct gating mechanisms. One mechanism partially closes Cx46 hemichannels from a fully open state, γ(open), to a substate, γ(sub), about one-third of the conductance of γ(open); these transitions occur when the cell is depolarized to inside positive voltages, consistent with gating by transjunctional voltage in Cx46 gap junctions. The other gating mechanism closes Cx46 hemichannels to a fully closed state, γ(closed), on hyperpolarization to inside negative voltages and has unusual characteristics; transitions between γ(closed) and γ(open) appear slow (10-20 ms), often involving several transient substates distinct from γ(sub). The polarity of activation and kinetics of this latter form of gating indicate that it is the mechanism by which these hemichannels open in the cell surface membrane when unapposed by another hemichannel. Cx46 hemichannels display a substantial preference for cations over anions, yet have a large unitary conductance (~300 pS) and a relatively large pore as inferred from permeability to tetraethylammonium (~8.5 Å diameter). These hemichannels open at physiological voltages and could induce substantial cation fluxes in cells expressing Cx46.
AB - Gap junction channels are formed by members of the connexin gene family and mediate direct intercellular communication through linked hemichannels (connexons) from each of two adjacent cells. While for most connexins, the hemichannels appear to require an apposing hemichannel to open, macroscopic currents obtained from Xenopus oocytes expressing rat Cx46 suggested that some hemichannels can be readily opened by membrane depolarization [Paul, D. L., Ebihara, L., Takemoto, L. J., Swenson, K. I. and Goodenough, D. A. (1991), J. Cell Biol. 115, 1077-1089]. Here we demonstrate by single channel recording that hemichannels comprised of rat Cx46 exhibit complex voltage gating consistent with there being two distinct gating mechanisms. One mechanism partially closes Cx46 hemichannels from a fully open state, γ(open), to a substate, γ(sub), about one-third of the conductance of γ(open); these transitions occur when the cell is depolarized to inside positive voltages, consistent with gating by transjunctional voltage in Cx46 gap junctions. The other gating mechanism closes Cx46 hemichannels to a fully closed state, γ(closed), on hyperpolarization to inside negative voltages and has unusual characteristics; transitions between γ(closed) and γ(open) appear slow (10-20 ms), often involving several transient substates distinct from γ(sub). The polarity of activation and kinetics of this latter form of gating indicate that it is the mechanism by which these hemichannels open in the cell surface membrane when unapposed by another hemichannel. Cx46 hemichannels display a substantial preference for cations over anions, yet have a large unitary conductance (~300 pS) and a relatively large pore as inferred from permeability to tetraethylammonium (~8.5 Å diameter). These hemichannels open at physiological voltages and could induce substantial cation fluxes in cells expressing Cx46.
KW - connexins
KW - intercellular communication
KW - ion channels
KW - permeability
KW - rectification
UR - http://www.scopus.com/inward/record.url?scp=0029905253&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029905253&partnerID=8YFLogxK
U2 - 10.1073/pnas.93.12.5836
DO - 10.1073/pnas.93.12.5836
M3 - Article
C2 - 8650179
AN - SCOPUS:0029905253
SN - 0027-8424
VL - 93
SP - 5836
EP - 5841
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
ER -