Calmodulin regulates the trafficking of KCNQ2 potassium channels

• Published in: The FASEB journal Vol. 22; no. 4; pp. 1135 - 1143
• Main Authors: Etxeberria, Ainhoa, Aivar, Paloma, Rodriguez-Alfaro, Jose Angel, Alaimo, Alessandro, Villacé, Patricia, Gómez-Posada, Juan Camilo, Areso, Pilar, Villarroel, Alvaro
• Format: Journal Article
• Language: English
• Published: United States The Federation of American Societies for Experimental Biology 01-04-2008; Federation of American Societies for Experimental Biology
• Subjects: benign familial neonatal convulsions; BFNC; Calcium - metabolism; Calmodulin - metabolism; Cell Membrane - metabolism; Cells, Cultured; channelopathies; Endoplasmic Reticulum - metabolism; epilepsy; Humans; KCNQ2 Potassium Channel - metabolism; KCNQ3 Potassium Channel - metabolism; Kv7; Mutation; Patch-Clamp Techniques; Protein Transport
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.07-9712com

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 Ca²⁺-binding incompetent calmodulin or sequestering of calmodulin promotes the retention of wild-type channels in the ER. Thus, a direct interaction with Ca²⁺-calmodulin appears to be critical for the correct activity of KCNQ2 potassium channels as it controls the channels' exit from the ER.--Etxeberria, A., Aivar, P., Rodriguez-Alfaro, J. A., Alaimo, A., Villacé, P., Gómez-Posada, J. C., Areso, P., Villarroel, A. Calmodulin regulates the trafficking of KCNQ2 potassium channels.