A ring of eight conserved negatively charged amino acids doubles the conductance of BK channels and prevents inward rectification

Abstract

Large-conductance Ca²⁺–voltage-activated K⁺ channels (BK channels) control many key physiological processes, such as neurotransmitter release and muscle contraction. A signature feature of BK channels is that they have the largest single channel conductance of all K⁺ channels. Here we examine the mechanism of this large conductance. Comparison of the sequence of BK channels to lower-conductance K⁺ channels and to a crystallized bacterial K⁺ channel (MthK) revealed that BK channels have a ring of eight negatively charged glutamate residues at the entrance to the intracellular vestibule. This ring of charge, which is absent in lower-conductance K⁺ channels, is shown to double the conductance of BK channels for outward currents by increasing the concentration of K⁺ in the vestibule through an electrostatic mechanism. Removing the ring of charge converts BK channels to inwardly rectifying channels. Thus, a simple electrostatic mechanism contributes to the large conductance of BK channels.