Abstract
The phenomenon of desensitization is universal, but its mechanism is still ill-understood and controversial. A recently published study [Lin, F. & Stevens, C. F. (1994) J. Neurosci, 14, 2153-2160] attempted to cast light on the mechanism of desensitization of N-methyl-D-aspartate (NMDA) receptors, in particular the vexed question of whether the channel must open before it can desensitize. During the desensitizing preexposure to agonist in those experiments, more desensitization was produced when channel openings were observed than when no openings were observed. The conclusion that "desensitization occurs more rapidly from the open state" unfortunately was based on a stochastic fallacy, and we present here a theoretical treatment and illustration showing that the observed behavior is predicted by a simple mechanism in which desensitization can occur only from a shut state.
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- Colquhoun D., Hawkes A. G. A note on correlations in single ion channel records. Proc R Soc Lond B Biol Sci. 1987 Feb 23;230(1258):15–52. doi: 10.1098/rspb.1987.0008. [DOI] [PubMed] [Google Scholar]
- Colquhoun D., Hawkes A. G. On the stochastic properties of bursts of single ion channel openings and of clusters of bursts. Philos Trans R Soc Lond B Biol Sci. 1982 Dec 24;300(1098):1–59. doi: 10.1098/rstb.1982.0156. [DOI] [PubMed] [Google Scholar]
- Edmonds B., Colquhoun D. Rapid decay of averaged single-channel NMDA receptor activations recorded at low agonist concentration. Proc Biol Sci. 1992 Dec 22;250(1329):279–286. doi: 10.1098/rspb.1992.0160. [DOI] [PubMed] [Google Scholar]
- Edmonds B., Gibb A. J., Colquhoun D. Mechanisms of activation of glutamate receptors and the time course of excitatory synaptic currents. Annu Rev Physiol. 1995;57:495–519. doi: 10.1146/annurev.ph.57.030195.002431. [DOI] [PubMed] [Google Scholar]
- Lester R. A., Jahr C. E. NMDA channel behavior depends on agonist affinity. J Neurosci. 1992 Feb;12(2):635–643. doi: 10.1523/JNEUROSCI.12-02-00635.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lin F., Stevens C. F. Both open and closed NMDA receptor channels desensitize. J Neurosci. 1994 Apr;14(4):2153–2160. doi: 10.1523/JNEUROSCI.14-04-02153.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lin F., Stevens C. F. Both open and closed NMDA receptor channels desensitize. J Neurosci. 1994 Apr;14(4):2153–2160. doi: 10.1523/JNEUROSCI.14-04-02153.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]