The ability of the Kv7.1 potassium channel to sense external potassium ions depends essentially on the charge of the E290 residue.
Identified residue E290 as essential for Kv7.1 potassium channel sensitivity to external potassium, providing molecular insights into mechanisms that, when mutated, can cause long QT syndrome.
Kv7.1 voltage-gated K(+) (Kv) channels are present in the apical membranes of marginal cells of the stria vascularis of the inner ear, where they mediate K(+) efflux into the scala media (cochlear duct) of the cochlea. As such, they are exposed to the K(+)-rich (∼ 150 mM of external K(+) (K(+) e)) environment of the endolymph. Previous studies have shown that Kv7.1 currents are substantially suppressed by high K(+) e (independent of the effects of altering the electrochemical gradient). However, the molecular basis for this inhibition, which is believed to involve stabilization of an inactivated state, remains unclear. Using sequence alignment of S5-pore linkers of several Kv channels, we identified a key residue, E290, found in only a few Kv channels including Kv7.1. We used substituted cysteine accessibility methods and patch-clamp analysis to provide evidence that the ability of Kv7.1 to sense K(+) e depends on E290, and that the charge at this position is essential for Kv7.1's K(+) e sensitivity. We propose that Kv7.1 may use this feedback mechanism to maintain the magnitude of the endocochlear potential, which boosts the driving force to generate the receptor potential of hair cells. The implications of our findings transcend the auditory system; mutations at this position also result in long QT syndrome in the heart.
Wang et al. (Mon,) reported a other. E290 residue substitution was evaluated on Sensitivity to external potassium ions (K+ e). The ability of the Kv7.1 potassium channel to sense external potassium ions depends essentially on the charge of the E290 residue.