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This Article Full Text Full Text (PDF) All Versions of this Article: 97/1/93    most recent 01047.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Guo, X. Articles by Lester, R. A. J. Search for Related Content PubMed PubMed Citation Articles by Guo, X. Articles by Lester, R. A. J.

Regulation of Nicotinic Acetylcholine Receptor Desensitization by Ca²⁺

¹Department of Neurobiology, McKnight Brain Institute, ²Civitan International Research Center, and the ³Vision Science Graduate Program, University of Alabama at Birmingham, Birmingham, Alabama

Submitted 4 October 2005; accepted in final form 11 October 2006

The relationship between the concentration of intracellular Ca²⁺ ([Ca²⁺]_i) and recovery from desensitization of nicotinic acetylcholine receptors (nAChRs) in rat medial habenula (MHb) neurons was investigated using the whole cell patch-clamp techniques in combination with microfluoresecent [Ca²⁺]_i measurements. Recovery from desensitization was assessed with a paired-pulse agonist application protocol. Application of 100 µM nicotine (5 s) caused pronounced desensitization of nAChRs, after which recovery proceeded with two components. The relative weight of the two phases of recovery was sensitive to the nature of the intracellular Ca²⁺ chelator, with a greater fraction of channels recovering during the fast phase in the presence of BAPTA than EGTA. Recovery was affected by differential Ca²⁺ buffering only when Ca²⁺ was present in the extracellular solution, implying that Ca²⁺ influx through nAChRs was responsible for slowing the recovery. Simultaneous [Ca²⁺]_i measurements showed that recovery from desensitization was inversely correlated with the instantaneous [Ca²⁺]_i, further supporting the suggestion that elevation of [Ca²⁺]_i limits the return of nAChRs to the resting state. In a separate set of experiments, activation of voltage-gated Ca²⁺ channels during the recovery phase produced a sufficiently large increase in [Ca²⁺]_i to reduce recovery from desensitization even in the absence of Ca²⁺ influx through nAChRs. Overall, it is suggested that Ca²⁺ entry through both nAChRs and voltage-gated Ca²⁺ channels exerts a negative feedback on nAChR activity through stabilization of desensitized states. The interaction of these two Ca²⁺ sources could form the basis of a coincidence detector under specific circumstances.

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