Up-Regulation of the Large-Conductance Ca2+-Activated K+ Channel by Glycogen Synthase Kinase GSK3 beta

作者：Fezai Myriam; Ahmed Musaab; Hosseinzadeh Zohreh; Lang Florian^*

来源：Cellular Physiology and Biochemistry, 2016, 39(3): 1031-1039.

DOI：10.1159/000447810

• Large conductance Ca2+-activated K+ channel
• Glycogen synthase kinase 3 beta
• Voltage clamp Lithium
• Neuronal excitation

Background/Aims: The pleotropic functions of the large conductance Ca2+-activated K+ channels (maxi K+ channel or BK channels) include regulation of neuronal excitation and cell volume. Kinases participating in those functions include the glycogen synthase kinase GSK3 beta which is under negative control of protein kinase B (PKB/Akt). GSK3 beta is inhibited by the antidepressant Lithium. The present study thus explored whether GSK3 beta modifies the activity of BK channels. Methods: cRNA encoding the Ca2+ insensitive BK channel mutant BKM513I+Delta 899-903 was injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type GSK3 beta, inactive (K85R)GSK3 beta, or wild-type GSK3 beta with wild-type PKB. K+ channel activity was measured utilizing dual electrode voltage clamp. Results: BK channel activity in BKM513I+Delta 899-903 expressing oocytes was significantly increased by co-expression of GSK3 beta, but not by co-expression of (K85R)GSK3 beta. The effect of wild type GSK3 beta was abrogated by additional co-expression of wild-type PKB and by 24 hours incubation with Lithium (1 mM). Disruption of channel insertion into the cell membrane by brefeldin A (5 mu M) was followed by a decline of the current to a similar extent in oocytes expressing BK and GSK3 beta and in oocytes expressing BK alone. Conclusion: GSK3 beta may up-regulate BK channels, an effect disrupted by Lithium or additional expression of PKB and possibly participating in the regulation of cell volume and excitability.

• 出版日期2016