Preferred Formation of Heteromeric Channels between Coexpressed SK1 and IKCa Channel Subunits Provides a Unique Pharmacological Profile of Ca2+-Activated Potassium Channels (original) (raw)
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The European journal of neuroscience, 2015
The activation of small conductance calcium-dependent (SK) channels regulates membrane excitability by causing membrane hyperpolarization. Three subtypes (SK1-3) have been cloned, with each subtype expressed within the nervous system. The locations of channel subunits overlap, with SK1 and SK2 subunits often expressed in the same brain region. We showed that expressed homomeric rat SK1 subunits did not form functional channels, because subunits accumulated in the Golgi. This raised the question of whether heteromeric channels could form with SK1 subunits. The co-expression of SK1 and SK2 subunits in HEK293 cells preferentially co-assembled to produce heteromeric channels with a fixed stoichiometry of alternating subunits. The expression in hippocampal CA1 neurons of mutant rat SK1 subunits [rat SK1(LV213/4YA)] that produced an apamin-sensitive current changed the amplitude and pharmacology of the medium afterhyperpolarization. The overexpression of rat SK1(LV213/4YA) subunits reduce...
Channelopathy of small- and intermediate-conductance Ca2+-activated K+ channels
Acta Pharmacologica Sinica
Part of the Medical Genetics Commons, and the Medicinal and Pharmaceutical Chemistry Commons Channelopathy of Small-and Intermediate-Conductance Ca Channelopathy of Small-and Intermediate-Conductance Ca 2+ 2+-activated K-activated K + + Channels Channels Comments Comments This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Acta Pharmacologica Sinica in 2022 following peer review. The final publication may differ and is available at Springer via
Pharmacological Reviews, 2005
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The Journal of General Physiology, 1999
Coexpression of the β subunit (KV,Caβ) with the α subunit of mammalian large conductance Ca2+- activated K+(BK) channels greatly increases the apparent Ca2+sensitivity of the channel. Using single-channel analysis to investigate the mechanism for this increase, we found that the β subunit increased open probability (Po) by increasing burst duration 20–100-fold, while having little effect on the durations of the gaps (closed intervals) between bursts or on the numbers of detected open and closed states entered during gating. The effect of the β subunit was not equivalent to raising intracellular Ca2+in the absence of the beta subunit, suggesting that the β subunit does not act by increasing all the Ca2+binding rates proportionally. The β subunit also inhibited transitions to subconductance levels. It is the retention of the BK channel in the bursting states by the β subunit that increases the apparent Ca2+sensitivity of the channel. In the presence of the β subunit, each burst of ope...
Structure, Gating and Basic Functions of the Ca2+-activated K Channel of Intermediate Conductance
Current neuropharmacology, 2018
The KCa3.1 channel is the intermediate-conductance member of the Ca2+- activated K channel superfamily. It is widely expressed in excitable and non-excitable cells, where it plays a major role in a number of cell functions. This paper aims at illustrating the main structural, biophysical and modulatory properties of the KCa3.1 channel, and providing an account of experimental data on its role in volume regulation and Ca2+ signals. Research and online content related to the structure, structure/function relationship, and physiological role of the KCa3.1 channel are reviewed. Expressed in excitable and non-excitable cells, the KCa3.1 channel is voltage independent, its opening being exclusively gated by the binding of intracellular Ca2+ to calmodulin, a Ca2+- binding protein constitutively associated with the C-terminus of each KCa3.1 channel α subunit. The KCa3.1 channel activates upon high affinity Ca2+ binding, and in highly coordinated fashion giving steep Hill functions and relat...