Alcohol withdrawal is associated with a downregulation of large-conductance Ca²⁺-activated K⁺ channels in rat inferior colliculus neurons

酒精戒断与大鼠下丘神经元大电导 Ca²⁺ 激活 K⁺ 通道下调有关

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作者:Prosper N'Gouemo, Martin Morad

Conclusions

The downregulation of BK(Ca) channels outlasts the finite period of elevated susceptibility to alcohol withdrawal seizures. These findings indicate that BK(Ca) channels, per se, may not be fundamentally important for the generation of alcohol withdrawal seizures.

Methods

Outward K⁺ currents and BK(Ca) channel proteins were measured using the whole cell configuration of patch clamp techniques and Western blot analysis, respectively.

Results

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 (BK(Ca)) 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 BK(Ca) channels also was significantly reduced in IC neurons at 24 and 48 h following alcohol withdrawal. Conclusions: The downregulation of BK(Ca) channels outlasts the finite period of elevated susceptibility to alcohol withdrawal seizures. These findings indicate that BK(Ca) channels, per se, may not be fundamentally important for the generation of alcohol withdrawal seizures.

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