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Subunit Assembly and Domain Analysis of Electrically Silent K + Channel α‐Subunits of the Rat Kv9 Subfamily
Author(s) -
Stocker Martin,
Hellwig Michaela,
Kerschensteiner Daniel
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.721725.x
Subject(s) - subfamily , protein subunit , heterologous expression , potassium channel , biology , amino acid , microbiology and biotechnology , biophysics , g alpha subunit , electrophysiology , alpha (finance) , c terminus , cys loop receptors , biochemistry , receptor , neuroscience , recombinant dna , gene , acetylcholine receptor , medicine , construct validity , nursing , nicotinic acetylcholine receptor , patient satisfaction
α‐Subunits of the voltage‐gated potassium channel (Kv) subfamily Kv9 show no channel activity after homomultimeric expression in heterologous expression systems. This report shows that heteromultimeric expression of rKv9.1 and rKv9.3 specifically suppresses the currents mediated by α‐subunits of the Kv2 and Kv3 subfamilies but does not affect currents mediated by α‐subunits of the Kv1 and Kv4 subfamilies. To understand the molecular basis of the electrical silence of Kv9 homomultimeric channels, crucial functional domains (amino and carboxy terminus, S4 segment, and pore region) were exchanged between Kv9 α‐subunits and rKv1.3. Electrophysiological studies of these chimeras revealed that the pore region is involved in determining the nonconductive behavior of homomultimeric Kv9 channels. This analysis was extended by protein interaction assays, aiming to identify the region of Kv9 subunits responsible for the specific suppression of rKv2.1‐ and rKv3.4‐mediated currents. We could show that the amino‐terminal domain of Kv9 α‐subunits does not support homomultimeric assembly but interacts specifically with the rKv2.1 amino‐terminal region. Conversely, the specific intersubfamily assembly of rKv3.4 with rKv9.1 or rKv9.3 is governed by the hydrophobic core and not the amino‐terminal domain.