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Mefloquine Effects on the Lens Suggest Cooperative Gating of Gap Junction Channels

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Abstract

Mefloquine (MFQ) selectively blocks exogenously expressed gap junction channels composed of C×50 but not C×46. The purpose of the current study was to evaluate MFQ effects on wild-type (WT) mouse lenses that express both C×50 and C×46 in their outer shell of differentiating fibers (DFs). Lenses in which C×46 was knocked into both C×50 alleles (KI) were used as controls; MFQ had no effect on coupling in these lenses. When WT lenses were exposed to MFQ, the DF coupling conductance decreased significantly, suggesting that C×50 contributes about 57% of the coupling conductance in DF and C×46 contributes 43%. Remarkably, in the presence of MFQ, the 43% of the channels that remained open did not gate closed in response to a reduction in pH, whereas in the absence of MFQ, the same pH change caused all the DF channels to gate closed. Since MFQ is a selective blocker of C×50 channels, it appears that C×46 channels lack pH-mediated gating in the absence of functional C×50 channels but are pH-sensitive in the presence of C×50 channels. These results suggest the two types of channels interact and gate cooperatively.

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Acknowledgement

This work was supported by National Eye Institute grants EY06391, EY13163 and EY13869.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, State University of New York, Stony Brook, NY, 11794-8661, USA

    Francisco J. Martinez-Wittinghan, Caterina Sellitto, Thomas W. White & Richard T. Mathias

  2. Department of Biological Sciences, College of Optometry, State University of New York, 33 West 42nd Street, New York, NY, 10036, USA

    Miduturu Srinivas

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  1. Francisco J. Martinez-Wittinghan
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  2. Miduturu Srinivas
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  3. Caterina Sellitto
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  4. Thomas W. White
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  5. Richard T. Mathias
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Correspondence to Richard T. Mathias.

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Martinez-Wittinghan, F.J., Srinivas, M., Sellitto, C. et al. Mefloquine Effects on the Lens Suggest Cooperative Gating of Gap Junction Channels. J Membrane Biol 211, 163–171 (2006). https://doi.org/10.1007/s00232-006-0021-6

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  • DOI: https://doi.org/10.1007/s00232-006-0021-6

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