High-Conductance Calcium-Activated Potassium Channels in Rat Brain: Pharmacology, Distribution, and Subunit Composition
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- 作者：Siegmund G. Wanner ; Robert O. Koch ; Alexandra Koschak ; Maria Trieb ; Maria L. Garcia ; Gregory J. Kaczorowski ; and Hans-Gü ; nther Knaus
- 刊名：Biochemistry
- 出版年：1999
- 出版时间：April 27, 1999
- 年：1999
- 卷：38
- 期：17
- 页码：5392 - 5400
- 全文大小：195K
- 年卷期：v.38,no.17(April 27, 1999)
- ISSN：1520-4995
文摘
In rat brain, high-conductance Ca2+-activated K+ (BK) channels are targeted to axons andnerve terminals [Knaus, H. G., et al. (1996) J. Neurosci. 16, 955-963], but absolute levels of their regionalexpression and subunit composition have not yet been fully established. To investigate these issues, anIbTX analogue ([125I]IbTX-D19Y/Y36F) was employed that selectively binds to neuronal BK channelswith high affinity (Kd = 21 pM). Cross-linking experiments with [125I]IbTX-D19Y/Y36F in the presenceof a bifunctional reagent led to covalent incorporation of radioactivity into a protein with an apparentmolecular mass of 25 kDa. Deglycosylation and immunoprecipitation studies with antibodies raised against
- and smooth muscle 
-subunits of the BK channel suggest that the -subunit that is associated with theneuronal BK channel is a novel protein. Quantitative receptor autoradiography reveals the highest levelsof BK channel expression in the outer layers of the neocortex, hippocampal perforant path projections,and the interpeduncular nucleus. This distribution pattern has also been confirmed in immunocytochemicalexperiments with a BK channel-selective antibody. Taken together, these findings imply that neuronalBK channels exhibit a restricted distribution in brain and have a subunit composition different from thoseof their smooth muscle congeners.
- and smooth muscle -subunits of the BK channel suggest that the -subunit that is associated with theneuronal BK channel is a novel protein. Quantitative receptor autoradiography reveals the highest levelsof BK channel expression in the outer layers of the neocortex, hippocampal perforant path projections,and the interpeduncular nucleus. This distribution pattern has also been confirmed in immunocytochemicalexperiments with a BK channel-selective antibody. Taken together, these findings imply that neuronalBK channels exhibit a restricted distribution in brain and have a subunit composition different from thoseof their smooth muscle congeners.