Epilepsy-associated mutations in the voltage sensor of KCNQ3 affect voltage dependence of channel opening.

ABSTRACT: One of the major factors known to cause neuronal hyperexcitability is malfunction of the potassium channels formed by KCNQ2 and KCNQ3. These channel subunits underlie the M current, which regulates neuronal excitability. Here, I investigate the molecular mechanisms by which epilepsy-associated mutations in the voltage sensor (S4) of KCNQ3 cause channel malfunction. Voltage clamp fluorometry reveals that the R230C mutation in KCNQ3 allows S4 movement but shifts the open/closed transition of the gate to very negative potentials. This results in the mutated channel remaining open throughout the physiological voltage range. Substitution of R230 with natural and unnatural amino acids indicates that the functional effect of the arginine residue at position 230 depends on both its positive charge

SUBMITTER: Barro-Soria R 

PROVIDER: S-EPMC6363412 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature