Phosphatidic acid modulation of Kv channel voltage sensor function

  1. Richard K Hite
  2. Joel A Butterwick
  3. Roderick MacKinnon  Is a corresponding author
  1. Howard Hughes Medical Institute, Rockefeller University, United States
8 figures

Figures

Figure 1 with 1 supplement
POPA modifies Kv channel gating.

(A) Representative family of currents recorded from Kv channels in DPhPC bilayers. Voltage is stepped from a holding voltage of −110 mV to increasingly more positive depolarization voltages (−110 mV …

https://doi.org/10.7554/eLife.04366.003
Figure 1—figure supplement 1
Representative families of currents recorded from Kv channels.

Representative families of currents recorded from Kv channels in (A) DPhPC:POPC (3:1) bilayers, (B) DPhPC:POPE (3:1) bilayers, (C) DPhPC:POPG (3:1) bilayers, (D) DPhPC:POPS (3:1) bilayers, (E) …

https://doi.org/10.7554/eLife.04366.004
Figure 2 with 1 supplement
Concentration dependence of Kv channel activation by POPA.

(A) Normalized tail currents (mean ± SEM) from current families recorded from Kv channels in DPhPC:POPA mixtures are fit with Boltzmann functions (DPhPC Vmid = −71 ± 1 mV, Z = 4.2, N = 8; DPhPC:POPA …

https://doi.org/10.7554/eLife.04366.005
Figure 2—figure supplement 1
Representative families of currents recorded from Kv channels.

Representative families of currents recorded from Kv channels in (A) DPhPC bilayers, (B) DPhPC:POPA (19:1) bilayers, (C) DPhPC:POPA (9:1) bilayers, (D) DPhPC:POPA (3:1) bilayers, (E) DPhPC:POPA …

https://doi.org/10.7554/eLife.04366.006
Figure 3 with 1 supplement
Concentration dependence of Kv channel activation by phospholipids.

(A) Plot of Vmid determined from a fit of tail currents to the Boltzmann equation vs phospholipid mole fraction for Kv channels in bilayers containing DPhPC:POPA (red), DPhPC:POPC (black), …

https://doi.org/10.7554/eLife.04366.007
Figure 3—figure supplement 1
Representative families of currents recorded from Kv channels.

Representative families of currents recorded from Kv channels in (A) DPhPC:DMPA (3:1) bilayers, (B) DPhPC:DOPA (3:1) bilayers, (C) DPhPC:BrPOPA (3:1) bilayers, (D) DPhPC:DOPMe (3:1) bilayers, (E) …

https://doi.org/10.7554/eLife.04366.008
Figure 4 with 1 supplement
Kv activation in Phospholipase D1-treated DPhPC bilayers.

(A) Normalized tail currents from representative current families recorded from Kv channels in a DPhPC bilayer (black–outside-out facing channels, Vmid = −72 mV; red–inside-out facing channels, Vmid

https://doi.org/10.7554/eLife.04366.009
Figure 4—figure supplement 1
Representative families of currents recorded from Kv channels in Phospholipase D1-treated DPhPC bilayers.

Representative families of currents recorded from Kv channels in DPhPC bilayers (A) 0 and (B) 40 min after addition of 50 units/ml S. chromofuscus phospholipase D1 to the extracellular side of the …

https://doi.org/10.7554/eLife.04366.010
Kv activation in DPhPC bilayers fused with phospholipid vesicles.

(A) Normalized tail currents from representative current families recorded from Kv channels in a DPhPC bilayer before (black, Vmid = −65 mV) and after fusion of POPA vesicles to the extracellular …

https://doi.org/10.7554/eLife.04366.011
Surface charge voltage offset in phospholipid membranes.

(A) In symmetric membranes lacking charged phospholipids, Vmem, the voltage to which channels respond, is equal to the command voltage, Vi − Vo, set on the amplifier. (B) In asymmetric membranes …

https://doi.org/10.7554/eLife.04366.012
Figure 7 with 1 supplement
Phosphatidic acid modifies KvAP activation.

(A) Normalized tail currents (mean ± SEM) from current families recorded from KvAP in DPhPC bilayers (black, Vmid = −25 ± 1 mV, Z = 2.6, N = 8), DPhPC:DPhPA (1:1) bilayers (red, Vmid = −6 ± 1 mV, Z …

https://doi.org/10.7554/eLife.04366.013
Figure 7—figure supplement 1
Representative families of currents recorded from KvAP channels.

Representative families of currents recorded from Kv channels in (A) DPhPC bilayers, (B) DPhPC:DPhPA (1:1) bilayers, (C) DPhPC:POPA (3:1) bilayers. Voltage is stepped from a holding voltage of −100 …

https://doi.org/10.7554/eLife.04366.014
Structure and sequence alignment of Kv voltage sensor domains.

(A) View from the membrane plane of the voltage sensor domains of rat Kv1.2–2.1 paddle chimera and KvAP. The S4 transmembrane helices and their positively charged residues are highlighted in yellow. …

https://doi.org/10.7554/eLife.04366.015

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