Compartmentalized beta subunit distribution determines characteristics and ethanol sensitivity of somatic, dendritic, and terminal large-conductance calcium-activated potassium channels in the rat central nervous system
Department of Psychiatry
Medical Subject Headings
Animals; Calcium; Central Nervous System; Dendrites; Ethanol; Hypothalamo-Hypophyseal System; Ion Channel Gating; Kinetics; Large-Conductance Calcium-Activated Potassium Channel beta; Subunits; Large-Conductance Calcium-Activated Potassium Channels; inhibitors; Membrane Potentials; Neurons; Peptides; Presynaptic Terminals; Rats; Rats, Sprague-Dawley; Supraoptic Nucleus; Toxins, Biological
Life Sciences | Medicine and Health Sciences | Neuroscience and Neurobiology
Neurons are highly differentiated and polarized cells, whose various functions depend upon the compartmentalization of ion channels. The rat hypothalamic-neurohypophysial system (HNS), in which cell bodies and dendrites reside in the hypothalamus, physically separated from their nerve terminals in the neurohypophysis, provides a particularly powerful preparation in which to study the distribution and regional properties of ion channel proteins. Using electrophysiological and immunohistochemical techniques, we characterized the large-conductance calcium-activated potassium (BK) channel in each of the three primary compartments (soma, dendrite, and terminal) of HNS neurons. We found that dendritic BK channels, in common with somatic channels but in contrast to nerve terminal channels, are insensitive to iberiotoxin. Furthermore, analysis of dendritic BK channel gating kinetics indicates that they, like somatic channels, have fast activation kinetics, in contrast to the slow gating of terminal channels. Dendritic and somatic channels are also more sensitive to calcium and have a greater conductance than terminal channels. Finally, although terminal BK channels are highly potentiated by ethanol, somatic and dendritic channels are insensitive to the drug. The biophysical and pharmacological properties of somatic and dendritic versus nerve terminal channels are consistent with the characteristics of exogenously expressed alphabeta1 versus alphabeta4 channels, respectively. Therefore, one possible explanation for our findings is a selective distribution of auxiliary beta1 subunits to the somatic and dendritic compartments and beta4 to the terminal compartment. This hypothesis is supported immunohistochemically by the appearance of distinct punctate beta1 or beta4 channel clusters in the membrane of somatic and dendritic or nerve terminal compartments, respectively.
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Citation: J Pharmacol Exp Ther. 2009 Jun;329(3):978-86. Epub 2009 Mar 25. Link to article on publisher's site