Lysine-rich extracellular rings formed by hbeta2 subunits confer the outward rectification of BK channels.
The auxiliary beta subunits of large-conductance Ca(2+)-activated K(+) (BK) channels greatly contribute to the diversity of BK (mSlo1 alpha) channels, which is fundamental to the adequate function in many tissues. Here we describe a functional element of the extracellular segment of hbeta2 auxiliary subunits that acts as the positively charged rings to modify the BK channel conductance. Four consecutive lysines of the hbeta2 extracellular loop, which reside sufficiently close to the extracellular entryway of the pore, constitute three positively charged rings. These rings can decrease the extracellular K(+) concentration and prevent the Charybdotoxin (ChTX) from approaching the extracellular entrance of channels through electrostatic mechanism, leading to the reduction of K(+) inflow or the outward rectification of BK channels. Our results demonstrate that the lysine rings formed by the hbeta2 auxiliary subunits influences the inward current of BK channels, providing a mechanism by which current can be rapidly diminished during cellular repolarization. Furthermore, this study will be helpful to understand the functional diversity of BK channels contributed by different auxiliary beta subunits.
Chen
Maorong
M
Key Laboratory of Molecular Biophysics, Huazhong University of Science and Technology, Ministry of Education, College of Life Science and Technology, Wuhan, Hubei, China.
Gan
Geliang
G
Wu
Ying
Y
Wang
Lu
L
Wu
Yingliang
Y
Ding
Jiuping
J
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D000939:Epitopes / Q000494:pharmacology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000187:drug effects / Q000502:physiology; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000187:drug effects / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000502:physiology*; D008239:Lysine / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D021122:Protein Subunits / Q000502:physiology; D055672:Static Electricity
D000939:Epitopes; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010446:Peptide Fragments; D021122:Protein Subunits; D018999:Charybdotoxin; D008239:Lysine; D011188:Potassium; D002118:Calcium