Effect of substituting amino acids in extracellular disulfide loop on GABA rho1 subunit function

Brain Research
L Lu

Abstract

Common features of GABA receptor/channels include a large extracellular NH2-terminal region that is the receptor domain, and four putative transmembrane segments that contribute to form the channel. A conserved Cys-Cys loop of the NH2-terminal domain in GABA receptor/channels is essential for maintaining the receptor and channel function. It has been suggested by other investigators that alteration of amino acids between these two cystines may affect the channel open kinetics. To investigate the mechanism underlying ligand binding and channel open, we have substituted several amino acids in the Cys-Cys loop of the GABA rho1 subunit and for the first time demonstrated the effect of mutations in the Cys-Cys loop on the single-channel kinetics of the rho1 subunit. For example, a single substitution of Arg198 in the extracellular Cys-Cys loop with Ala or Lys significantly reduced both the maximal amplitude of the whole-cell current and the single-channel open probability (Po). Single channel kinetics of mutants revealed no long open state, without changes in the short open state. There was a shift of apparent half-activation concentration (EC50) between the control and mutants in response to GABA. Our data further suggest that the ...Continue Reading

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Citations

Apr 21, 1999·Brain Research. Brain Research Reviews·A K Mehta, M K Ticku
Dec 3, 1999·The Journal of Physiology·V E WotringD S Weiss

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