Wu Xiaoan, Cunningham Kevin P, Bruening-Wright Andrew, Pandey Shilpi, Larsson H Peter
Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
School of Life Sciences, University of Westminster, London W1W 6UW, UK.
Int J Mol Sci. 2024 Apr 13;25(8):4309. doi: 10.3390/ijms25084309.
Voltage-gated potassium (Kv) channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels share similar structures but have opposite gating polarity. Kv channels have a strong coupling (>10) between the voltage sensor (S4) and the activation gate: when S4s are activated, the gate is open to >80% but, when S4s are deactivated, the gate is open <10 of the time. Using noise analysis, we show that the coupling between S4 and the gate is <200 in HCN channels. In addition, using voltage clamp fluorometry, locking the gate open in a Kv channel drastically altered the energetics of S4 movement. In contrast, locking the gate open or decreasing the coupling between S4 and the gate in HCN channels had only minor effects on the energetics of S4 movement, consistent with a weak coupling between S4 and the gate. We propose that this loose coupling is a prerequisite for the reversed voltage gating in HCN channels.
电压门控钾（Kv）通道和超极化激活的环核苷酸门控（HCN）通道具有相似的结构，但门控极性相反。Kv通道在电压传感器（S4）和激活门之间具有很强的耦合作用（>10）：当S4被激活时，门打开的概率>80%，但当S4失活时，门打开的时间<10%。通过噪声分析，我们发现HCN通道中S4与门之间的耦合作用<200。此外，使用电压钳荧光法，在Kv通道中锁定门打开会极大地改变S4运动的能量学。相比之下，在HCN通道中锁定门打开或降低S4与门之间的耦合作用对S4运动的能量学只有轻微影响，这与S4与门之间的弱耦合一致。我们认为这种松散耦合是HCN通道中反向电压门控的先决条件。
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