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 interface 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 conducts 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 whether the ability of Kv2.1 to conduct Na+ reflected unique properties of either its S5-S6 loop or channel domains that held the S5-S6 loop in place (the scaffolding), we studied chimeras made from Kv1.3 (which is completely impermeable 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 highly selective K+ channels that conducted Na+ and displayed competition between Na+ and K+ for conduction through the pore: In channels that contained the S5-S6 loop from Kv2.1, concentration-dependent block of Na+ current by either 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+ to conduct through the channel. Furthermore, these results indicate that the competitive interaction between K+ and Na+ at the selectivity filter is determined not only by the S5-S6 loop but also by the scaffolding that holds the S5-S6 loop.
Immke
D
D
Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269, USA.
Kiss
L
L
LoTurco
J
J
Korn
S J
SJ
D002412:Cations / Q000378:metabolism; D002460:Cell Line; D002463:Cell Membrane Permeability; D051668:Delayed Rectifier Potassium Channels; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics*; D051664:Kv1.3 Potassium Channel; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins / Q000378:metabolism; D051669:Shab Potassium Channels; D012964:Sodium / Q000378:metabolism
D002412:Cations; D051668:Delayed Rectifier Potassium Channels; C496973:KCNA3 protein, human; C496988:KCNB1 protein, human; D051664:Kv1.3 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D051669:Shab Potassium Channels; D012964:Sodium; D011188:Potassium