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Separation of P/C‐ and U‐type inactivation pathways in Kv1.5 potassium channels
Author(s) -
Kurata Harley T.,
Doerksen Kyle W.,
Eldstrom Jodene R.,
Rezazadeh Saman,
Fedida David
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.087148
Subject(s) - biophysics , extracellular , chemistry , potassium channel , mutant , potassium , ion channel , membrane potential , biochemistry , biology , receptor , gene , organic chemistry
P/C‐type inactivation of Kv channels is thought to involve conformational changes in the outer pore of the channel, culminating in a partial constriction of the selectivity filter. Recent studies have identified a number of phenotypic differences in the inactivation properties of different Kv channels, including different sensitivities to elevation of extracellular K + concentration, and different state dependencies of inactivation. We have demonstrated that an alternatively spliced short form of Kv1.5, resulting in disruption of the T1 domain, exhibits a shift in the state dependence of inactivation in this channel, and in the current study we have examined this further to contrast the properties of inactivation from open versus closed states. In a TEA + ‐sensitive mutant of Kv1.5 (Kv1.5 R487T), 10 m m extracellular TEA + inhibits inactivation in both full‐length and T1‐deleted channels, but does not inhibit closed‐state inactivation in T1‐deleted channel forms. Similarly, substitution of K + and Na + with Cs + ions in the recording medium inhibits inactivation of both full‐length and T1‐deleted channel forms, but fails to inhibit closed‐state inactivation of T1‐deleted channels. Collectively, these data distinguish between open‐state and closed‐state inactivation, and suggest the presence of multiple possible mechanisms of inactivation coexisting in Kv1 channels.