Alcohol withdrawal is associated with a downregulation of large-conductance Ca2+-activated K+ channels in rat inferior colliculus neurons
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Large conductance calcium-activated potassium (BKCa or KCa1.1) channels are well-known molecular targets for the action of alcohol and therefore may play an important role in the pathogenesis of alcohol withdrawal syndrome.
We evaluate the modifications of total outward K+ currents and protein expression of BKCa channels α-subunit in inferior colliculus (IC) neurons obtained from controls and rats subjected to alcohol withdrawal associated with enhanced susceptibility to seizures.
Outward K+ currents and BKCa channel proteins were measured using the whole cell configuration of patch clamp techniques and Western blot analysis, respectively.
Total outward K+ current density was significantly reduced in IC neurons at 24 and 48 h during the alcohol withdrawal period when the susceptibility to seizures was maximal and absent, respectively. The iberiotoxin-sensitive (BKCa) current density and conductance also were significantly reduced at 24 h following alcohol withdrawal. Consistent with functional data, the levels of protein expression of α-subunit associated with BKCa channels also was significantly reduced in IC neurons at 24 and 48 h following alcohol withdrawal.
The downregulation of BKCa channels outlasts the finite period of elevated susceptibility to alcohol withdrawal seizures. These findings indicate that BKCa channels, per se, may not be fundamentally important for the generation of alcohol withdrawal seizures.
KeywordsAlcohol withdrawal BKCa channels Iberiotoxin Outward current density Protein Seizures
This publication was made possible by Public Health Service grants (NS047193 and AA020073 to P.N., and HL62525 to M.M.) from the National Institutes of Health (NIH), and its contents are the responsibility of the authors and do not necessary represent the official views of NIH. All the experimental procedures used in this study were in accordance with the National Research Council’s Guide for Care and Use of Laboratory Animals and approved by the Georgetown University Animal Care and Use Committee.
Conflict of interest
The authors declare no conflict of interest.
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