PubMed 17993630

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ2 , Kv7.2

Title: Calmodulin regulates the trafficking of KCNQ2 potassium channels.

Authors: Ainhoa Etxeberria, Paloma Aivar, Jose Angel Rodriguez-Alfaro, Alessandro Alaimo, Patricia Villacé, Juan Camilo Gómez-Posada, Pilar Areso, Alvaro Villarroel

Journal, date & volume: FASEB J., 2008 Apr , 22, 1135-43

PubMed link:

Voltage-dependent potassium KCNQ2 (Kv7.2) channels play a prominent role in the control of neuronal excitability. These channels must associate with calmodulin to function correctly and, indeed, a mutation (R353G) that impairs this association provokes the onset of a form of human neonatal epilepsy known as benign familial neonatal convulsions (BFNC). We show here that perturbation of calmodulin binding leads to endoplasmic reticulum (ER) retention of KCNQ2, reducing the number of channels that reach the plasma membrane. Interestingly, elevating the expression of calmodulin in the BFNC mutant partially restores the intracellular distribution of the KCNQ channel. In contrast, overexpression of a Ca(2+)-binding incompetent calmodulin or sequestering of calmodulin promotes the retention of wild-type channels in the ER. Thus, a direct interaction with Ca(2+)-calmodulin appears to be critical for the correct activity of KCNQ2 potassium channels as it controls the channels' exit from the ER.