Control of ionic selectivity by a pore helix residue in the Kv1.2 channel

Abstract

Interaction between the selectivity filter and the adjacent pore helix of voltage-gated K+ (Kv) channels controls pore stability during K+ conduction. Kv channels, having their selectivity filter destabilized during depolarization, are said to undergo C-type inactivation. We examined the functionality of a residue at the pore helix of the Kv1.2 channel (V370), which reportedly affects C-type inactivation. A mutation into glycine (V370G) caused a shift in reversal potential from around -72 to -9 mV. The permeability ratios (P-Na/P-K) of the wild type and V370G mutant are 0.04 and 0.76, respectively. In the wild-type, P-Rb/P-K, P-Cs/P-K and P-Li/P-K are 0.78, 0.10 and 0.05, respectively. Kv1.2 V370G channels had enhanced permeability to Rb+ and Cs+ (P-Rb/P-K and P-Cs/P-K are 1.63 and 1.18, respectively); however, Li+ permeability was not significantly augmented (P-Li/P-K is 0.13). Therefore, in addition to its known effect on pore stability, V370 of Kv1.2 is also crucial in controlling ion selectivity.