TY - JOUR
T1 - Functional regulation of BK potassium channels by γ1 auxiliary subunits
AU - Gonzalez-Perez, Vivian
AU - Xia, Xiao Ming
AU - Lingle, Christopher J.
PY - 2014/4/1
Y1 - 2014/4/1
N2 - Many K+ channels are oligomeric complexes with intrinsic structural symmetry arising from the homo-tetrameric core of their pore-forming subunits. Allosteric regulation of tetramerically symmetric proteins, whether by intrinsic sensing domains or associated auxiliary subunits, often mirrors the fourfold structural symmetry. Here, through patch-clamp recordings of channel population ensembles and also single channels, we examine regulation of the Ca2+- and voltage-activated large conductance Ca2+- activated K+ (BK) channel by associated γ1-subunits. Through expression of differing ratios of γ1:α-subunits, the results reveal an all-or-none functional regulation of BK channels by γ-subunits: channels either exhibit a full gating shift or no shift at all. Furthermore, the γ1- induced shift exhibits a state-dependent labile behavior that recapitulates the fully shifted or unshifted behavior. The γ1-induced shift contrasts markedly to the incremental shifts in BK gating produced by 1-4 β-subunits and adds a new layer of complexity to the mechanisms by which BK channel functional diversity is generated.
AB - Many K+ channels are oligomeric complexes with intrinsic structural symmetry arising from the homo-tetrameric core of their pore-forming subunits. Allosteric regulation of tetramerically symmetric proteins, whether by intrinsic sensing domains or associated auxiliary subunits, often mirrors the fourfold structural symmetry. Here, through patch-clamp recordings of channel population ensembles and also single channels, we examine regulation of the Ca2+- and voltage-activated large conductance Ca2+- activated K+ (BK) channel by associated γ1-subunits. Through expression of differing ratios of γ1:α-subunits, the results reveal an all-or-none functional regulation of BK channels by γ-subunits: channels either exhibit a full gating shift or no shift at all. Furthermore, the γ1- induced shift exhibits a state-dependent labile behavior that recapitulates the fully shifted or unshifted behavior. The γ1-induced shift contrasts markedly to the incremental shifts in BK gating produced by 1-4 β-subunits and adds a new layer of complexity to the mechanisms by which BK channel functional diversity is generated.
KW - Allostery
KW - Asymmetry
KW - Slo1 channels
UR - http://www.scopus.com/inward/record.url?scp=84897476762&partnerID=8YFLogxK
U2 - 10.1073/pnas.1322123111
DO - 10.1073/pnas.1322123111
M3 - Article
C2 - 24639523
AN - SCOPUS:84897476762
SN - 0027-8424
VL - 111
SP - 4868
EP - 4873
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -