K ions exert a structural effect that brings stability to K selective pores. Thus, upon bathing Shab channels in 0 K solutions the ion conductance, G, irreversibly collapses. Related to this, studies with isolated KcsA channels have suggested that there is a transition [K] around which the pore takes one of two conformations, either the low (non-conducting) or high K (conducting) crystal structures. We examined this premise by looking at the K-dependency of G stability of Shab channels within the cell membrane environment. We found that: K effect on G stability is highly asymmetrical, and that as internal K is replaced by Na G drops in a way that suggests a transition internal [K]. Additionally, we found that external permeant ions inhibit G drop with a potency that differs from the global selectivity-sequence of K pores; the non-permeant TEA inhibited G drop in a K-dependent manner. Upon lowering internal [K] we observed an influx of Na at negative potentials. Na influx was halted by physiological external [K], which also restored G stability. Hyperpolarized potentials afforded G stability but, as expected, do not restore G selectivity. For completeness, Na interaction with Shab was also assessed at depolarized potentials by looking at Na block followed by permeation (pore unblock) at positive potentials, in solutions approaching the 0 K limit. The stabilizing effect of negative potentials along with the non-parallel variation of Na permeability and conductance-stability herein reported, show that pore stability and selectivity, although related, are not strictly coupled.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555546PMC
http://dx.doi.org/10.1080/19336950.2021.1993037DOI Listing

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