TY - JOUR
T1 - Regulation of BK channels by auxiliary γ subunits
AU - Zhang, Jiyuan
AU - Yan, Jiusheng
N1 - Publisher Copyright:
© 2014 Zhang and Yan.
PY - 2014
Y1 - 2014
N2 - The large-conductance, calcium- and voltage-activated potassium (BK) channel has the largest single-channel conductance among potassium channels and can be activated by both membrane depolarization and increases in intracellular calcium concentration. BK channels consist of pore-forming, voltage- and calcium-sensing a subunits, either alone or in association with regulatory subunits. BK channels are widely expressed in various tissues and cells including both excitable and non-excitable cells and display diverse biophysical and pharmacological characteristics. This diversity can be explained in part by posttranslational modifications and alternative splicing of the a subunit, which is encoded by a single gene, KCNMA1, as well as by tissue-specific ß subunit modulation. Recently, a leucine-rich repeat-containing membrane protein, LRRC26, was found to interact with BK channels and cause an unprecedented large negative shift (~-140 mV) in the voltage dependence of the BK channel activation. LRRC26 allows BK channels to open even at near-physiological calcium concentration and membrane voltage in non-excitable cells. Three LRRC26-related proteins, LRRC52, LRRC55, and LRRC38, were subsequently identified as BK channel modulators. These LRRC proteins are structurally and functionally distinct from the BK channel ß subunits and were designated as γ subunits. The discovery of the γ subunits adds a new dimension to BK channel regulation and improves our understanding of the physiological functions of BK channels in various tissues and cell types. Unlike BK channel ß subunits, which have been intensively investigated both mechanistically and physiologically, our understanding of the γ subunits is very limited at this stage. This article reviews the structure, modulatory mechanisms, physiological relevance, and potential therapeutic implications of γ subunits as they are currently understood.
AB - The large-conductance, calcium- and voltage-activated potassium (BK) channel has the largest single-channel conductance among potassium channels and can be activated by both membrane depolarization and increases in intracellular calcium concentration. BK channels consist of pore-forming, voltage- and calcium-sensing a subunits, either alone or in association with regulatory subunits. BK channels are widely expressed in various tissues and cells including both excitable and non-excitable cells and display diverse biophysical and pharmacological characteristics. This diversity can be explained in part by posttranslational modifications and alternative splicing of the a subunit, which is encoded by a single gene, KCNMA1, as well as by tissue-specific ß subunit modulation. Recently, a leucine-rich repeat-containing membrane protein, LRRC26, was found to interact with BK channels and cause an unprecedented large negative shift (~-140 mV) in the voltage dependence of the BK channel activation. LRRC26 allows BK channels to open even at near-physiological calcium concentration and membrane voltage in non-excitable cells. Three LRRC26-related proteins, LRRC52, LRRC55, and LRRC38, were subsequently identified as BK channel modulators. These LRRC proteins are structurally and functionally distinct from the BK channel ß subunits and were designated as γ subunits. The discovery of the γ subunits adds a new dimension to BK channel regulation and improves our understanding of the physiological functions of BK channels in various tissues and cell types. Unlike BK channel ß subunits, which have been intensively investigated both mechanistically and physiologically, our understanding of the γ subunits is very limited at this stage. This article reviews the structure, modulatory mechanisms, physiological relevance, and potential therapeutic implications of γ subunits as they are currently understood.
KW - Accessory protein
KW - Auxiliary subunit
KW - BK channels
KW - K
KW - KCNMA1
KW - Modulation
KW - Regulation
KW - Slo1
UR - http://www.scopus.com/inward/record.url?scp=84908363276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908363276&partnerID=8YFLogxK
U2 - 10.3389/fphys.2014.00401
DO - 10.3389/fphys.2014.00401
M3 - Review article
C2 - 25360119
AN - SCOPUS:84908363276
SN - 1664-042X
VL - 5
JO - Frontiers in Physiology
JF - Frontiers in Physiology
IS - OCT
M1 - 401
ER -