Introduction

The human BK channel (AKA Big K⁺ channel) is characterized by its distinctly high conductance of K⁺ through the cell membrane. They take part in many physiological activities like neuronal excitability, smooth muscle contraction and hair cell tuning. It works as a negative feedback regulator component which causes the neuronal cell to hyperpolarize when one or both variables reach a certain threshold (dual regulation is a key aspect of this channel):

1: The Ca²⁺ concentration.

2: The  membrane voltage.

It is composed roughly out of three domains:

The integral membrane pore and selectivity filter which is shared by all K⁺ channels (this fact is subsequently exploited when the CTD information is combined with the TM information) and is formed between the intervening domains of S5 and S6.

The integral membrane voltage sensor domains present in voltage-dependant channels (large homology between voltage gated channels) which is formed by the transmembrane segments S1 to S4.

The cytoplasmic domain which accounts for about two thirds of the protein and contains the tools that allows it to sense Ca²⁺ concentrations.

Fig. 1. Left: Simple representation of a BK channel monomer. The BK channel contains four identical subunits, each comprising seven transmembrane segments and a large intracellular C terminus. Right: Ribbon representation of a single subunit from the BK model. (Both images have been adapted from Peng's Yuan, et. al's paper)

In this paper, the authors have attempted to build the structure of the BK channel through the use of an x-ray crystal structure of 3 angstroms resolution of the gating apparatus (CTD) to construct the CTD monomer. In order to determine how these CTD monomers form a tetramer, the authors used molecular replacement against an x-ray diffraction pattern of a Slo2.2 chicken homologue which had been elucidated at a resolution of 6.0 angstroms. 

Once the postulated tetramer of the CTD was obtained, the authors superimposed the paddle chimera (voltage dependant potassium channel found in rats) structure onto the MthK channel (a bacterial homologue found in Methanobacterium thermoautotrophicum). Then the human BK channel CTD tetramer was superimposed over the MthK channel. This allowed the authors to create a speculative model for the complete structure of the human BK channel.

Fig. 2: Left:The tetrameric structure of the Human BK channel (adapted from Peng's Yuan, et. al's paper); Centre: the octameric structure of MthK potassium channel (created in PyMol); Right: tetrameric structure of paddle chimera (created in PyMol)