The Role of K Ions in Opening K Channels

Abstract

Baker, Hodgkin, and Meves (J Physiol, 170:541-560, 1964) found that with low internal K+, the voltage dependence of gNa is far right-shifted, allowing large action potentials from a resting potential of ∼ 0 mV. gK activation is also shifted. They considered the possibility that negative internal surface charge was unmasked at low internal ionic strength. Structural information suggests an alternative. In a closed voltage-gated K+ channel the S6 segments of the gate region are packed together and stabilized by van der Waals force, making the gate too small to accommodate a K+ ion with one hydration shell (∼8 A). The gate, when closed, is locked by the S4 segments in their full inward position. After full activation of all S4s, the gate region expands to accommodate a hydrated K+ ion. We postulate that an opening gate is first wetted as water penetrates, and is held open by a flow of K+ ions passing through. K+ is essential for holding the gate open, like a foot in the door: in an open channel the gate is occupied almost continuously by a K+ ion. Using Shaker K+ channels without inactivation, ∼0 mM K+ internally, 140 mM NaCl + 4mM KCl outside, we measured gK from tail currents. Our results indicate that with no K+ inside the voltage for 10% activation is right shifted by ∼10 mV, and the voltage for 90% activation by ∼45mV; i.e., the g-V curve is right shifted and much shallower. The results support the importance of K+ ions in opening the activation gate and keeping it open.