Previous studies have shown that the V j-dependent gating behavior of gap junction channels is altered by CO2 exposure. V j-dependent channel closure is increased by CO2 in some connexin channels and decreased in others. Since the former type of channels gate on the relatively negative side by V j (negative gaters) and the latter at the positive side (positive gaters), it has been hypothesized that gating polarity determines the way CO2 affects V j closure. To test this hypothesis, we have studied the CO2-mediated changes in V j gating in channels made of Cx32, Cx26, or a Cx32 mutant (Cx32-N2D) in which asparagine (N) at position 2 was replaced with aspartate (D). With exposure to CO2, Cx32 channels (negative gaters) show increased V j-dependent closure, whereas Cx26 channels (positive gaters) respond in the opposite way to V j. Additionally, Cx32-N2D channels (positive gaters) show decreased V j closure with exposure to CO2. The reciprocal Cx26 mutant, Cx26-D2N (negative gater), could not be tested because it did not express functional homotypic channels. The data support the hypothesis that polarity of fast V j gating determines whether CO2 increases or decreases the V j dependent closure of gap junction channels.
The Journal of Membrane Biology – Springer Journals
Published: Jan 1, 2004
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