Table 6.
Changes in HV1 properties in S4 (197–218) mutants versus WT channels
MutantSpeciesExpr. systemI?τactτtailΔVthrΔpH slopeSelectivityOtherReference
E196C CiHV1 [A246C] Xenopus TEVC Yes      MTSo open>closed Gonzalez et al., 2010  
L198C CiHV1 [I248C] Xenopus TEVC Yes      MTSo open>closed Gonzalez et al., 2010  
G199C CiHV1 [G249C] Xenopus i-o Yes   2    Mony et al., 2015  
L200W CiHV1 [L250W] Xenopus TEVC Yes 0.27 0.67     Okuda et al., 2016  
L200W/ΔC CiHV1 [L250W/ΔC] Xenopus TEVC Yes 0.20 0.019     Okuda et al., 2016  
I202C CiHV1 [V252C] Xenopus TEVC Yes      MTSo open>closed Gonzalez et al., 2010  
R205A hHV1 HEK wc Yes 0.0053 0.086 −1 48  0.63 × WT gating chargea Ramsey et al., 2006, 2010 
R205A hHV1 Vesicle flux       Δ H+ fluxb Letts, 2014  
R205Hc/T222stop hHV1 COS wc Yes     H+ Accessible to external Zn2+ Kulleperuma et al., 2013  
R205Q Mouse [R201Q] HEK wc Yes Faster  −50   1.36 × WT gating chargea Sasaki et al., 2006  
R205N CiHV1 [R255N] Xenopus i-o Yes      0.33 × WT gating charged Gonzalez et al., 2013  
R205N CiHV1 [R255N] Xenopus TEVC Yes   −36   0.78 × WT gating chargea Chamberlin et al., 2014  
R205C CiHV1 [R255C] Xenopus TEVC Yes   −37   1.3 × WT gating chargea Chamberlin et al., 2014  
R205A/R208A hHV1 HEK wc Yes   128 51   Ramsey et al., 2010  
R205A/R211A hHV1 HEK wc Yes   96 45   Ramsey et al., 2010  
L206C CiHV1 [L256C] Xenopus TEVC Yes      No MTSo/i access Gonzalez et al., 2010  
W207A,c W207S,c or W207Fc hHV1 HEK/COS wc Yes 0.01 0.034 −17.9 40 H+ Loss of selectivity at pHo > 8 Cherny et al., 2015  
W207I Mouse [W203I] HEK wc Yes 0.019 0.059    Tandem dimer Okuda et al., 2016  
W207A, W207S, or W207F kHV1 [W176A, W176S, W176F] HEK/COS wc Yes 0.025   40 H+  Cherny et al., 2015  
W207A, W207S, or W207F EhHV1 [W278A, W278S, W278F] HEK/COS wc Yes 0.2  −28.2 50 H+  Cherny et al., 2015  
W207I CiHV1 [W257I] Xenopus TEVC Yes 0.29 0.030     Okuda et al., 2016  
W207I/A210A CiHV1 [W257I/F260A] Xenopus TEVC Yes 0.23 0.026     Okuda et al., 2016  
R208A hHV1 HEK wc Yes 0.0965 0.075 7 45   Ramsey et al., 2006, 2010 
R208A hHV1 Vesicle flux       Δ H+ fluxb Letts, 2014  
R208A hHV1 Xenopus i-o No       Hong et al., 2014  
R208K hHV1 Xenopus i-o Yes   −40   1.7 × WT gating chargea Hong et al., 2014  
R208K hHV1 HEK/COS wc Yes     H+  Dudev et al., 2015  
R208Hc/T222stop hHV1 COS wc Yes     H+ Accessible to external & maybe internal Zn2+ Kulleperuma et al., 2013  
R208Q hHV1 Xenopus i-o No       Hong et al., 2014  
R208Q Mouse [R204Q] HEK wc No       Sasaki et al., 2006  
R208N hHV1 Xenopus i-o No       Hong et al., 2014  
R208N CiHV1 [R258N] Xenopus i-o Yes      0.50 × WT gating charged Gonzalez et al., 2013  
R208C CiHV1 [R258C] Xenopus TEVC Yes   −10   0.87 × WT gating chargea Chamberlin et al., 2014  
V209C CiHV1 [V259C] Xenopus TEVC Yes      No MTSo/i access Gonzalez et al., 2010  
R211A hHV1 HEK wc Yes 2.24 0.092 70 53   Ramsey et al., 2006, 2010  
R211A hHV1 Vesicle flux       Δ H+ fluxb Letts, 2014  
R211S hHV1 Xenopus i-o Yes   35   0.72 × WT gating chargea Hong et al., 2014  
R211S hHV1 Xenopus i-o Yes   87 49 Gu+ at pH 8//8 Berger and Isacoff, 2011  
R211S/I127C CiHV1 [R261S/I175C] Xenopus i-o Yes   15    Mony et al., 2015  
R211Hc/T222stop hHV1 COS wc Yes     H+ Accessible to internal Zn2+ when open Kulleperuma et al., 2013  
R211H/D112V/V116Dc hHV1 COS/HEK wc Yes      Accessible to internal Zn2+ when open Morgan et al., 2013  
R211Q mHV1 [R207Q] HEK wc Yes   nc    Sasaki et al., 2006  
R211N CiHV1 [R261N] Xenopus i-o Yes      0.38 × WT gating charged Gonzalez et al., 2013  
R211C CiHV1 [R261C] Xenopus TEVC Yes   54  H+ 0.78 × WT gating chargea Chamberlin et al., 2014  
R211C NpHv1 [R163C] HEK wc Yes     H+  Chaves et al., 2016  
I212C CiHV1 [I262C] Xenopus TEVC Yes      MTSi closed>open Gonzalez et al., 2010  
N214K hHV1 HEK wc Yes   −3 43  Inward rectification Ramsey et al., 2010  
N214R hHV1 HEK wc Yes   10 40  Inward rectification Ramsey et al., 2010  
N214R hHV1 Xenopus i-o No       Tombola et al., 2008  
N214A hHV1 HEK wc Yes   −3 42   Ramsey et al., 2010  
N214A hHV1 Vesicle flux       nc H+ flux Letts, 2014  
N214R mHV1 [N210R] HEK wc Yes Slow Very slow −V  H+  Sakata et al., 2010  
N214D hHV1 COS/HEK wc Yes     H+  Musset et al., 2011  
N214C CiHV1 [N264C] Xenopus TEVC Yes      MTSi closed>open Gonzalez et al., 2010  
G215A hHV1 COS/HEK wc Yes  Fast   H+  Musset et al., 2011  
I217stop mHV1 [I213stop] HEK wc Yes       Sakata et al., 2010  
G215stop mHV1 [G211stop] HEK wc Yes       Sakata et al., 2010  
I213stop mHV1 [I209stop] HEK wc Yes       Sakata et al., 2010  
A210stop mHV1 [A206stop] HEK wc Yes   +V  H+ τact has weak V dependence Sakata et al., 2010  
L204stop mHV1 [L200stop] HEK wc No       Sakata et al., 2010  
MutantSpeciesExpr. systemI?τactτtailΔVthrΔpH slopeSelectivityOtherReference
E196C CiHV1 [A246C] Xenopus TEVC Yes      MTSo open>closed Gonzalez et al., 2010  
L198C CiHV1 [I248C] Xenopus TEVC Yes      MTSo open>closed Gonzalez et al., 2010  
G199C CiHV1 [G249C] Xenopus i-o Yes   2    Mony et al., 2015  
L200W CiHV1 [L250W] Xenopus TEVC Yes 0.27 0.67     Okuda et al., 2016  
L200W/ΔC CiHV1 [L250W/ΔC] Xenopus TEVC Yes 0.20 0.019     Okuda et al., 2016  
I202C CiHV1 [V252C] Xenopus TEVC Yes      MTSo open>closed Gonzalez et al., 2010  
R205A hHV1 HEK wc Yes 0.0053 0.086 −1 48  0.63 × WT gating chargea Ramsey et al., 2006, 2010 
R205A hHV1 Vesicle flux       Δ H+ fluxb Letts, 2014  
R205Hc/T222stop hHV1 COS wc Yes     H+ Accessible to external Zn2+ Kulleperuma et al., 2013  
R205Q Mouse [R201Q] HEK wc Yes Faster  −50   1.36 × WT gating chargea Sasaki et al., 2006  
R205N CiHV1 [R255N] Xenopus i-o Yes      0.33 × WT gating charged Gonzalez et al., 2013  
R205N CiHV1 [R255N] Xenopus TEVC Yes   −36   0.78 × WT gating chargea Chamberlin et al., 2014  
R205C CiHV1 [R255C] Xenopus TEVC Yes   −37   1.3 × WT gating chargea Chamberlin et al., 2014  
R205A/R208A hHV1 HEK wc Yes   128 51   Ramsey et al., 2010  
R205A/R211A hHV1 HEK wc Yes   96 45   Ramsey et al., 2010  
L206C CiHV1 [L256C] Xenopus TEVC Yes      No MTSo/i access Gonzalez et al., 2010  
W207A,c W207S,c or W207Fc hHV1 HEK/COS wc Yes 0.01 0.034 −17.9 40 H+ Loss of selectivity at pHo > 8 Cherny et al., 2015  
W207I Mouse [W203I] HEK wc Yes 0.019 0.059    Tandem dimer Okuda et al., 2016  
W207A, W207S, or W207F kHV1 [W176A, W176S, W176F] HEK/COS wc Yes 0.025   40 H+  Cherny et al., 2015  
W207A, W207S, or W207F EhHV1 [W278A, W278S, W278F] HEK/COS wc Yes 0.2  −28.2 50 H+  Cherny et al., 2015  
W207I CiHV1 [W257I] Xenopus TEVC Yes 0.29 0.030     Okuda et al., 2016  
W207I/A210A CiHV1 [W257I/F260A] Xenopus TEVC Yes 0.23 0.026     Okuda et al., 2016  
R208A hHV1 HEK wc Yes 0.0965 0.075 7 45   Ramsey et al., 2006, 2010 
R208A hHV1 Vesicle flux       Δ H+ fluxb Letts, 2014  
R208A hHV1 Xenopus i-o No       Hong et al., 2014  
R208K hHV1 Xenopus i-o Yes   −40   1.7 × WT gating chargea Hong et al., 2014  
R208K hHV1 HEK/COS wc Yes     H+  Dudev et al., 2015  
R208Hc/T222stop hHV1 COS wc Yes     H+ Accessible to external & maybe internal Zn2+ Kulleperuma et al., 2013  
R208Q hHV1 Xenopus i-o No       Hong et al., 2014  
R208Q Mouse [R204Q] HEK wc No       Sasaki et al., 2006  
R208N hHV1 Xenopus i-o No       Hong et al., 2014  
R208N CiHV1 [R258N] Xenopus i-o Yes      0.50 × WT gating charged Gonzalez et al., 2013  
R208C CiHV1 [R258C] Xenopus TEVC Yes   −10   0.87 × WT gating chargea Chamberlin et al., 2014  
V209C CiHV1 [V259C] Xenopus TEVC Yes      No MTSo/i access Gonzalez et al., 2010  
R211A hHV1 HEK wc Yes 2.24 0.092 70 53   Ramsey et al., 2006, 2010  
R211A hHV1 Vesicle flux       Δ H+ fluxb Letts, 2014  
R211S hHV1 Xenopus i-o Yes   35   0.72 × WT gating chargea Hong et al., 2014  
R211S hHV1 Xenopus i-o Yes   87 49 Gu+ at pH 8//8 Berger and Isacoff, 2011  
R211S/I127C CiHV1 [R261S/I175C] Xenopus i-o Yes   15    Mony et al., 2015  
R211Hc/T222stop hHV1 COS wc Yes     H+ Accessible to internal Zn2+ when open Kulleperuma et al., 2013  
R211H/D112V/V116Dc hHV1 COS/HEK wc Yes      Accessible to internal Zn2+ when open Morgan et al., 2013  
R211Q mHV1 [R207Q] HEK wc Yes   nc    Sasaki et al., 2006  
R211N CiHV1 [R261N] Xenopus i-o Yes      0.38 × WT gating charged Gonzalez et al., 2013  
R211C CiHV1 [R261C] Xenopus TEVC Yes   54  H+ 0.78 × WT gating chargea Chamberlin et al., 2014  
R211C NpHv1 [R163C] HEK wc Yes     H+  Chaves et al., 2016  
I212C CiHV1 [I262C] Xenopus TEVC Yes      MTSi closed>open Gonzalez et al., 2010  
N214K hHV1 HEK wc Yes   −3 43  Inward rectification Ramsey et al., 2010  
N214R hHV1 HEK wc Yes   10 40  Inward rectification Ramsey et al., 2010  
N214R hHV1 Xenopus i-o No       Tombola et al., 2008  
N214A hHV1 HEK wc Yes   −3 42   Ramsey et al., 2010  
N214A hHV1 Vesicle flux       nc H+ flux Letts, 2014  
N214R mHV1 [N210R] HEK wc Yes Slow Very slow −V  H+  Sakata et al., 2010  
N214D hHV1 COS/HEK wc Yes     H+  Musset et al., 2011  
N214C CiHV1 [N264C] Xenopus TEVC Yes      MTSi closed>open Gonzalez et al., 2010  
G215A hHV1 COS/HEK wc Yes  Fast   H+  Musset et al., 2011  
I217stop mHV1 [I213stop] HEK wc Yes       Sakata et al., 2010  
G215stop mHV1 [G211stop] HEK wc Yes       Sakata et al., 2010  
I213stop mHV1 [I209stop] HEK wc Yes       Sakata et al., 2010  
A210stop mHV1 [A206stop] HEK wc Yes   +V  H+ τact has weak V dependence Sakata et al., 2010  
L204stop mHV1 [L200stop] HEK wc No       Sakata et al., 2010  

That numerical entries are shown does not imply that any given change was significant. Italicized mutant entries from nonhuman species show the hHV1 equivalent. HEK, HEK-293, HEK-293T, tsA, or HM1; COS, COS-7; Xenopus, Xenopus laevis oocyte; wc, whole cell; i-o, inside-out patch configuration; TEVC, two-electrode voltage clamp. Blank entries indicate that the parameter was not examined. nc, measured, but no change. Parameters are given relative to WT in each study. For I?, yes means currents are detectable. Time constants are ratios of mutant/WT. The ΔVthreshold value is the change in absolute position of the gH–V relationship versus WT. The ΔpH slope is the slope in millivolts of the relationship between Vthreshold (or other parameters reflecting the absolute position of the gH–V relationship) and Vrev or EH (which are not identical; see section Table entries defined). When C-terminal truncations are indicated as XNNNstop, this means STOP replaces X at position NNN; hence, position NNN and all subsequent residues are truncated, and the last position remaining is NNN-1. For column Other, MTS access from inside or outside (MTSi or MTSo, respectively) is listed as open>closed if the open channel was more accessible.

a

Slope factor of gH–V relationship.

b

Normal initial H+ flux followed by recovery ascribed to leak induced in vesicles.

c

In an H140A/H193A (Zn2+ insensitive) background.

d

By limiting slope method.

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