(A) Amino acid sequence alignment of Kv1.2, MthK, and hSlo1 (human BK) in the pore region. Alignment started from the T of the TVGYGD signature sequence of the selectivity filter. (B) PyMol-generated structure models of the BK channel pore region based on the Kv1.2 or the MthK structure. Equivalent BK amino acid residues were substituted into the Kv1.2 or MthK sequence. One of the four subunits was removed in the side view to reveal the pore. Top view is from the extracellular side of the channel. Bottom view is from the intracellular side of the channel. The M314 position in BK is highlighted in colors: green, C; blue, N; red, O; gold, S. (C; 1) Diagram of the closed-state charge interaction hypothesis, with the middle of the concentric circles representing the pore of the channel. Each one of the subunits had a substituted histidine. (2) Diagram of the open-state charge stabilization hypothesis.