Activation of a mechanosensitive BK channel by membrane stress created with amphipaths.
Some BK channels are activated in response to membrane stretch. However, it remains largely unknown which membrane component transmits forces to the channel and which part of the channel senses the force. Recently, we have shown that a BK channel cloned from chick heart (named SAKCa channel) is a stretch activated channel, while deletion of a 59 amino acids splice insert (STREX) located in the cytoplasmic side, abolishes its stretch-sensitivity. This finding raised a question whether stress in the bilayer is crucial for the mechanical activation of the channel. To address this question we examined the effects of membrane perturbing amphipaths on the stretch activation of the SAKCa channel and its STREX-deletion mutant. We found that both anionic amphipath trinitrophenol (TNP) and cationic amphipath chlorpromazine (CPZ) could dose-dependently activate the channel by leftward shifting the voltage activation curve when applied alone. In contrast, TNP and CPZ compensated each other's effect when applied sequentially. These results can be understood in the framework of the bilayer couple hypothesis, suggesting that stress in the plasma membrane can activate the SAKCa channel. Interestingly, the STREX-deletion mutant channel has much less sensitivity to the amphipaths, suggesting that STREX acts as an intermediate structure that can indirectly convey stress in the membrane to the gate of the SAKCa channel via an unidentified membrane associated protein(s) that can detect or transmit stress in the membrane.
Qi
Zhi
Z
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, 15 Datun Rd, Beijing, 100101, PR China.
Chi
Shaopeng
S
Su
Xueyan
X
Naruse
Keiji
K
Sokabe
Masahiro
M
D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D002645:Chickens; D002746:Chlorpromazine / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D018492:Dopamine Antagonists / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D010851:Picrates / Q000494:pharmacology*; D017384:Sequence Deletion; D013314:Stress, Mechanical; D014475:Uncoupling Agents / Q000494:pharmacology*
D018492:Dopamine Antagonists; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010851:Picrates; D014475:Uncoupling Agents; C005858:picric acid; D002746:Chlorpromazine