Key result
Mutation of the conserved cysteine 51 in the KCNK5 channel did not alter its functional expression, rectification properties, or pH dependence compared to the non-mutated channel.
The conserved extracellular cysteine C51 in the KCNK5 potassium channel forms a disulphide bridge that preserves dimeric structure but is not essential for channel activity.
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C51 disulfide is dispensable for KCNK5 function in expression systems; leaves open its role in native cardiac channels.
The functional channel unit of K(+) channels with two pore regions in tandem is thought to be a homodimer and it has been suggested that this dimeric structure occurs by interaction of an extracellular domain, the self-interacting domain. Interaction and functional assembly have been studied in some detail for KCNK1. It is proposed that a disulphide bond between highly conserved C69 residues of the self-interacting domain is formed which is essential for channel activity. We mutated C51, the equivalent residue in the pH-dependent KCNK5, to study its effect on channel function. Western analysis of proteins from cells expressing epitope-tagged KCNK5 and KCNK5-C51S was consistent with reduction-sensitive self-association of monomers dependent upon the presence of C51. Patch-clamp analysis of heterologously expressed KCNK5-C51S, however, revealed it was functional and indistinguishable in rectification properties and pH dependence from the non-mutated channel. The same result was found with KCNK5-C115S. It is concluded that the proposed disulphide bond between cysteine 51 residues of KCNK5 subunits does occur and preserves a dimeric structure in the detergent solubilized complex. Functional assays, on the other hand, suggest that such a disulphide bridge is not essential for correct functional expression.
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Niemeyer et al. (2003) studied this question. Mutation of C51 and C115 in KCNK5 (TASK-2) K+ channel vs. Non-mutated KCNK5 channel was evaluated on Channel function (rectification properties and pH dependence) and dimerization. Mutation of the conserved cysteine 51 in the KCNK5 channel did not alter its functional expression, rectification properties, or pH dependence compared to the non-mutated channel.
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