Influence of non-P region domains on selectivity filter properties in voltage-gated K+ channels

The selectivity filter in voltage-gated K+ channels is formed at the interf ace of the pore loops (S5-S6 loop) from four channel subunits, Whereas most K+ channels are essentially impermeable to Na+, the Kv2.1 K+ channel condu cts Na+ relatively well in the absence of K+ and selects for K+ over Na+ at least partially by an affinity-based competition mechanism. To examine whe ther the ability of Kv2.1 to conduct Na+ reflected unique properties of eit her its S5-S6 loop or channel domains that held the S5-S6 loop in place (th e scaffolding), we studied chimeras made from Kv1.3 (which is completely im permeable to Na+) and Kv2.1. Chimeras that contained either the S5-S6 loop from Kv1.3 inserted into the Kv2.1 scaffolding or vice versa both made high ly selective K+ channels that conducted Na+ and displayed competition betwe en Na+ and K+ for conduction through the pore. In channels that contained t he S5-S6 loop from Kv2.1, concentration-dependent block of Na+ current by e ither external or internal K+ differed depending on whether Kv2.1 or Kv1.3 donated the scaffolding. These results indicate that neither the S5-S6 loop nor the scaffolding from Kv2.1 possess unique attributes that permit Na+ t o conduct through the channel. Furthermore, these results indicate that the competitive interaction between K+ and Na+ at the selectivity filter is de termined not only by the S5-S6 loop but also by the scaffolding that holds the S5-S6 loop.