Introduction

Figure 1. Torpedo Ray (Torpedo Californica) (6)
Photo © Joe Belanger. See more of his photos here.

In the February issue of Nature, the elusive structure of the ClC Chloride channel made its monumental debut.  (7) Consummating a prolonged study, researchers led by principle investigator Roderick MacKinnon at Howard Hughes Medical Center at The Rockefeller University extrapolated the novel 3-d structure using X-ray crystallographic techiques. 

The structure of ClC chloride channels had been left unsettled for many years prior to this discovery.  The first ClC chloride channels were discovered by Miller and White in the electric organ of a Torpedo Ray (Torpedo californica). (18) Subsequently, in 1990 the first voltage gated ClC chloride channel was cloned by Jentsh et. al. who appropriately named it ClC-0 believing the had found what belonged to a series of anion channels. (18,6)

Due to their distinct properties a double barrel channel was predicted, however evidence of a single barrel architecture remained in contention. Following Miller's initial study, chloride channels were found in a variety of other species, including humans.  However, unresolved questions regarding its membrane topology, the molecular components of the pore, and the mechanism for the ClC chloride channel selectivity filter were still left to be anwered. (7) Specifically, those regarding gating properties, anion over cation selectivity, halogen permeability and coupling between gating and ion conduction.  

Figure 2. (Above) Proposed membrane topology of ClC Chloride channels according to biochemical analysis. There is a discrepancy regarding the hydrophobic region between D9 and D12, due to difficulties in carrying out these measurements experimentally. (9)

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Author: Pablo Bernardson
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