Alcohol withdrawal is associated with a downregulation of large-conductance Ca²⁺-activated K⁺ channels in rat inferior colliculus neurons.
Alcohol withdrawal is associated with a downregulation of large-conductance Ca²⁺-activated K⁺ channels in rat inferior colliculus neurons.
复制标题
酒精戒断与大鼠下丘神经元中大电导 Ca2+ 激活的 K+ 通道的下调有关。
DOI:
10.1007/s00213-013-3346-8
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发表时间:
2014
影响因子:
3.4
通讯作者:
Morad,Martin
中科院分区:
文献类型:
--
作者:
N'Gouemo,Prosper;Morad,Martin
RationaleLarge conductance calcium-activated potassium (BKCaor 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.ObjectivesWe evaluate the modifications of total outward K+currents and protein expression of BKCachannels α-subunit in inferior colliculus (IC) neurons obtained from controls and rats subjected to alcohol withdrawal associated with enhanced susceptibility to seizures.MethodsOutward K+currents and BKCachannel proteins were measured using the whole cell configuration of patch clamp techniques and Western blot analysis, respectively.ResultsTotal 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 BKCachannels also was significantly reduced in IC neurons at 24 and 48 h following alcohol withdrawal.ConclusionsThe downregulation of BKCachannels outlasts the finite period of elevated susceptibility to alcohol withdrawal seizures. These findings indicate that BKCachannels, per se, may not be fundamentally important for the generation of alcohol withdrawal seizures.