Electrostatic determinants of the ion channel control of the nicotinic acetylcholine receptor of Torpedo californica

A. Kukol, E. Neumann

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7 Citations (Scopus)


The patch clamp K+-conductance G of the nicotinic acetylcholine receptor (AcChoR) dimer (M(r)approximate to 590 000) of Torpedo californica, reconstituted in lipid vesicles, icles, which decreases with increasing Cain the range 0.1 less than or equal to[Ca2+]/mM less than or equal to 2, can be quantitatively rationalized by Ca2+-binding to negatively charged sites, causing charge reversal reducing the normal K+-accumulation in the channel vestibules. Cleavage of the sialic acid residues (up to 20+/-2 per dimer) reduces the K+-accumulation factor alpha=G(0)/G(infinity) from alpha=3+/-0.8 of the normal AcChoR to alpha=2+/-0.7 for the desialyated AcChoR. Desialysation also decreases the Ca2+-sensitivity of the conductance from G(0)=96.6+/-6 pS at [Ca2+]-->0 of the normal AcChoR to G(0)=84.2+/-6 pS. Endogenous hyperphosphorylation (to up to 28+/-4 phosphates per dimer) enhances the vestibular K+-accumulation to alpha=3.6+/-0.7, without affecting the Ca2+-dissociation equilibrium constant K-Ca = 0.34+/- 0.05 ntM at 295 K (22 degrees C). Most interestingly, even in the absence of AcCho, the hyperphosphorylated AcChoR dimer exhibits spontaneously long-lasting open channel events (tau= 200+/-50 ms). At [AcCho] = 2 mu M there are two open states (tau(1) =20+/-10 ms, tau(2) = 140+/-60 ms) whereas the normal AcChoR dimer has only one open state (tau = 6+/-4 ms). - Physiologically important is that (i) the sialic acid and phosphate residues render the AcChoR conductance sensitive to control by divalent ions and (ii) the channel behavior of the hyperphosphorylated AcChoR without AcCho appears to indicate pathophysiologically high phosphorylation activity of the cell leading, among others, to myasthenic syndromes.

Original languageEnglish
Pages (from-to)618-625
Number of pages8
JournalEuropean Biophysics Journal
Issue number6
Publication statusPublished - 1998


  • acetylcholine receptor
  • channel events
  • sialic acids
  • receptor phosphorylation


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