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Preferential assembly of heteromeric small conductance calcium‐activated potassium channels
Author(s) -
Church Timothy W.,
Weatherall Kate L.,
Corrêa Sonia A. L.,
Prole David L.,
Brown Jon T.,
Marrion Neil V.
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12789
Subject(s) - homomeric , apamin , sk channel , protein subunit , microbiology and biotechnology , calcium activated potassium channel , hek 293 cells , chemistry , hyperpolarization (physics) , afterhyperpolarization , biophysics , potassium channel , ion channel , biochemistry , biology , intracellular , stereochemistry , receptor , gene , nuclear magnetic resonance spectroscopy
The activation of small conductance calcium‐dependent ( SK ) channels regulates membrane excitability by causing membrane hyperpolarization. Three subtypes ( SK 1‐3) have been cloned, with each subtype expressed within the nervous system. The locations of channel subunits overlap, with SK 1 and SK 2 subunits often expressed in the same brain region. We showed that expressed homomeric rat SK 1 subunits did not form functional channels, because subunits accumulated in the Golgi. This raised the question of whether heteromeric channels could form with SK 1 subunits. The co‐expression of SK 1 and SK 2 subunits in HEK 293 cells preferentially co‐assembled to produce heteromeric channels with a fixed stoichiometry of alternating subunits. The expression in hippocampal CA 1 neurons of mutant rat SK 1 subunits [rat SK 1( LV 213/4 YA )] that produced an apamin‐sensitive current changed the amplitude and pharmacology of the medium afterhyperpolarization. The overexpression of rat SK 1( LV 213/4 YA ) subunits reduced the sensitivity of the medium afterhyperpolarization to apamin, substantiating the preferential co‐assembly of SK 1 and SK 2 subunits to form heteromeric channels. Species‐specific channel assembly occurred as the co‐expression of human SK 1 with rat SK 2 did not form functional heteromeric channels. The replacement of two amino acids within the C‐terminus of rat SK 2 with those from human SK 2 permitted the assembly of heteromeric channels when co‐expressed with human SK 1. These data showed that species‐specific co‐assembly was mediated by interaction between the C‐termini of SK channel subunits. The finding that SK channels preferentially co‐assembled to form heteromeric channels suggested that native heteromeric channels will predominate in cells expressing multiple SK channel subunits.