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. 1994 Feb;66(2 Pt 1):325–334. doi: 10.1016/s0006-3495(94)80781-7

Conductance mutations of the nicotinic acetylcholine receptor do not act by a simple electrostatic mechanism.

P Kienker 1, G Tomaselli 1, M Jurman 1, G Yellen 1
PMCID: PMC1275699  PMID: 8161686

Abstract

Fixed negative charges in many cation channels raise the single-channel conductance, apparently by an electrostatic mechanism: their effects are accentuated in solutions of low ionic strength and attenuated at high ionic strength. The charges of specific amino acids near the ends of the proposed pore-lining M2 segment of the nicotinic acetylcholine receptor, termed the extracellular and cytoplasmic rings, have recently been shown to influence the single-channel K+ conductance (Imoto, K., C. Busch, B. Sakmann, M. Mishina, T. Konno, J. Nakai, H. Bujo, Y. Mori, K. Fukuda and S. Numa. 1988. Nature 335:645-648). We examined whether these charges might act by a direct electrostatic effect on the energy of ions in the pore, rather than indirectly by inducing a structural change. To this end, we measured the conductances of charge mutants over a range of K+ concentrations (ionic strengths). As expected, we found that negative charge mutations raise the conductance, and positive charge mutations lower it. The effects of cytoplasmic-ring mutations are accentuated at low ionic strength, but they are not completely attenuated at high ionic strength. The effects of extracellular-ring mutations are independent of ionic strength. These results are inconsistent with the simplest electrostatic model. We suggest a modified model that qualitatively accounts for the data.

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Selected References

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