Key result
Slow inactivation alters Shaker potassium channel cavity conformation and decreases tetraethylammonium affinity.
The study demonstrates that the cavity of Shaker potassium channels undergoes a conformational change during slow inactivation, suggesting coupling between activation and slow-inactivation gates.
Findings remain preclinical and should not guide therapy; leaves open whether similar cavity changes occur during slow inactivation in human Kv channels.
Slow inactivation involves a local rearrangement of the outer mouth of voltage-gated potassium channels, but nothing is known regarding rearrangements in the cavity between the activation gate and the selectivity filter. We now report that the cavity undergoes a conformational change in the slow-inactivated state. This change is manifest as altered accessibility of residues facing the aqueous cavity and as a marked decrease in the affinity of tetraethylammonium for its internal binding site. These findings have implications for global alterations of the channel during slow inactivation and putative coupling between activation and slow-inactivation gates.
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Panyi et al. (2007) studied this question. The cavity of the Shaker potassium channel undergoes a conformational change in the slow-inactivated state, altering residue accessibility and decreasing tetraethylammonium affinity.
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