Key result
F(290) mutations in the Shaker K channel modify a final activation transition and deactivation kinetics, correlating with the hydrophobicity of the substituted residue.
A hydrophobic residue at position 290 in the Shaker K+ channel controls the energy barrier of the final gating transition, likely by regulating the transfer of the fourth gating charge (R371).
F290 selectively controls the final S4 arginine transition; leaves open whether this mechanism extends to cardiac Kv isoforms in vivo.
It is now well established that the voltage-sensor domains present in voltage-gated ion channels and some phosphatases operate by transferring several charged residues (gating charges), mainly arginines located in the S4 segment, across the electric field. The conserved phenylalanine F(290) located in the S2 segment of the Shaker K channel is an aromatic residue thought to interact with all the four gating arginines carried by the S4 segment and control their transfer [Tao X, et al. (2010) Science 328:67-73]. In this paper we study the possible interaction of the gating charges with this residue by directly detecting their movement with gating current measurements in 12 F(290) mutants. Most mutations do not significantly alter the first approximately 80-90% of the gating charge transfer nor the kinetics of the gating currents during activation. The effects of the F(290) mutants are (i) the modification of a final activation transition accounting for approximately 10-20% of the total charge, similar to the effect of the ILT mutant [Ledwell JL, et al. (1999) J Gen Physiol 113:389-414] and (ii) the modification of the kinetics of the gating charge movement during deactivation. These effects are well correlated with the hydrophobicity of the substituted residue, showing that a hydrophobic residue at position 290 controls the energy barrier of the final gating transition. Our results suggest that F(290) controls the transfer of R(371), the fourth gating charge, during gating while not affecting the movement of the other three gating arginines.
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Lacroix et al. (2011) studied this question. F(290) mutations in Shaker K channel vs. Wild type was evaluated on Gating charge transfer and kinetics. F(290) mutations in the Shaker K channel modify a final activation transition and deactivation kinetics, correlating with the hydrophobicity of the substituted residue.
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