Table 6. Changes in H V 1 properties in... | Rockefeller University Press

Table 6.

Changes in H_V1 properties in S4 (197–218) mutants versus WT channels

Mutant	Species	Expr. system	I?	τ_act	τ_tail	ΔV_thr	ΔpH slope	Selectivity	Other	Reference
E196C	CiH_V1 [A246C]	Xenopus TEVC	Yes						MTS_o open>closed	Gonzalez et al., 2010
L198C	CiH_V1 [I248C]	Xenopus TEVC	Yes						MTS_o open>closed	Gonzalez et al., 2010
G199C	CiH_V1 [G249C]	Xenopus i-o	Yes			2				Mony et al., 2015
L200W	CiH_V1 [L250W]	Xenopus TEVC	Yes	0.27	0.67					Okuda et al., 2016
L200W/ΔC	CiH_V1 [L250W/ΔC]	Xenopus TEVC	Yes	0.20	0.019					Okuda et al., 2016
I202C	CiH_V1 [V252C]	Xenopus TEVC	Yes						MTS_o open>closed	Gonzalez et al., 2010
R205A	hH_V1	HEK wc	Yes	0.0053	0.086	−1	48		0.63 × WT gating charge^{^a}	Ramsey et al., 2006, 2010
R205A	hH_V1	Vesicle flux							Δ H⁺ flux^{^b}	Letts, 2014
R205H^{^c}/T222stop	hH_V1	COS wc	Yes					H⁺	Accessible to external Zn²⁺	Kulleperuma et al., 2013
R205Q	Mouse [R201Q]	HEK wc	Yes	Faster		−50			1.36 × WT gating charge^{^a}	Sasaki et al., 2006
R205N	CiH_V1 [R255N]	Xenopus i-o	Yes						0.33 × WT gating charge^{^d}	Gonzalez et al., 2013
R205N	CiH_V1 [R255N]	Xenopus TEVC	Yes			−36			0.78 × WT gating charge^{^a}	Chamberlin et al., 2014
R205C	CiH_V1 [R255C]	Xenopus TEVC	Yes			−37			1.3 × WT gating charge^{^a}	Chamberlin et al., 2014
R205A/R208A	hH_V1	HEK wc	Yes			128	51			Ramsey et al., 2010
R205A/R211A	hH_V1	HEK wc	Yes			96	45			Ramsey et al., 2010
L206C	CiH_V1 [L256C]	Xenopus TEVC	Yes						No MTS_o/i access	Gonzalez et al., 2010
W207A,^{^c} W207S,^{^c} or W207F^{^c}	hH_V1	HEK/COS wc	Yes	0.01	0.034	−17.9	40	H⁺	Loss of selectivity at pH_o > 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	kH_V1 [W176A, W176S, W176F]	HEK/COS wc	Yes	0.025			40	H⁺		Cherny et al., 2015
W207A, W207S, or W207F	EhH_V1 [W278A, W278S, W278F]	HEK/COS wc	Yes	0.2		−28.2	50	H⁺		Cherny et al., 2015
W207I	CiH_V1 [W257I]	Xenopus TEVC	Yes	0.29	0.030					Okuda et al., 2016
W207I/A210A	CiH_V1 [W257I/F260A]	Xenopus TEVC	Yes	0.23	0.026					Okuda et al., 2016
R208A	hH_V1	HEK wc	Yes	0.0965	0.075	7	45			Ramsey et al., 2006, 2010
R208A	hH_V1	Vesicle flux							Δ H⁺ flux^{^b}	Letts, 2014
R208A	hH_V1	Xenopus i-o	No							Hong et al., 2014
R208K	hH_V1	Xenopus i-o	Yes			−40			1.7 × WT gating charge^{^a}	Hong et al., 2014
R208K	hH_V1	HEK/COS wc	Yes					H⁺		Dudev et al., 2015
R208H^{^c}/T222stop	hH_V1	COS wc	Yes					H⁺	Accessible to external & maybe internal Zn²⁺	Kulleperuma et al., 2013
R208Q	hH_V1	Xenopus i-o	No							Hong et al., 2014
R208Q	Mouse [R204Q]	HEK wc	No							Sasaki et al., 2006
R208N	hH_V1	Xenopus i-o	No							Hong et al., 2014
R208N	CiH_V1 [R258N]	Xenopus i-o	Yes						0.50 × WT gating charge^{^d}	Gonzalez et al., 2013
R208C	CiH_V1 [R258C]	Xenopus TEVC	Yes			−10			0.87 × WT gating charge^{^a}	Chamberlin et al., 2014
V209C	CiH_V1 [V259C]	Xenopus TEVC	Yes						No MTS_o/i access	Gonzalez et al., 2010
R211A	hH_V1	HEK wc	Yes	2.24	0.092	70	53			Ramsey et al., 2006, 2010
R211A	hH_V1	Vesicle flux							Δ H⁺ flux^{^b}	Letts, 2014
R211S	hH_V1	Xenopus i-o	Yes			35			0.72 × WT gating charge^{^a}	Hong et al., 2014
R211S	hH_V1	Xenopus i-o	Yes			87	49	Gu⁺	at pH 8//8	Berger and Isacoff, 2011
R211S/I127C	CiH_V1 [R261S/I175C]	Xenopus i-o	Yes			15				Mony et al., 2015
R211H^{^c}/T222stop	hH_V1	COS wc	Yes					H⁺	Accessible to internal Zn²⁺ when open	Kulleperuma et al., 2013
R211H/D112V/V116D^{^c}	hH_V1	COS/HEK wc	Yes						Accessible to internal Zn²⁺ when open	Morgan et al., 2013
R211Q	mH_V1 [R207Q]	HEK wc	Yes			nc				Sasaki et al., 2006
R211N	CiH_V1 [R261N]	Xenopus i-o	Yes						0.38 × WT gating charge^{^d}	Gonzalez et al., 2013
R211C	CiH_V1 [R261C]	Xenopus TEVC	Yes			54		H⁺	0.78 × WT gating charge^{^a}	Chamberlin et al., 2014
R211C	NpHv1 [R163C]	HEK wc	Yes					H⁺		Chaves et al., 2016
I212C	CiH_V1 [I262C]	Xenopus TEVC	Yes						MTS_i closed>open	Gonzalez et al., 2010
N214K	hH_V1	HEK wc	Yes			−3	43		Inward rectification	Ramsey et al., 2010
N214R	hH_V1	HEK wc	Yes			10	40		Inward rectification	Ramsey et al., 2010
N214R	hH_V1	Xenopus i-o	No							Tombola et al., 2008
N214A	hH_V1	HEK wc	Yes			−3	42			Ramsey et al., 2010
N214A	hH_V1	Vesicle flux							nc H⁺ flux	Letts, 2014
N214R	mH_V1 [N210R]	HEK wc	Yes	Slow	Very slow	−V		H⁺		Sakata et al., 2010
N214D	hH_V1	COS/HEK wc	Yes					H⁺		Musset et al., 2011
N214C	CiH_V1 [N264C]	Xenopus TEVC	Yes						MTS_i closed>open	Gonzalez et al., 2010
G215A	hH_V1	COS/HEK wc	Yes		Fast			H⁺		Musset et al., 2011
I217stop	mH_V1 [I213stop]	HEK wc	Yes							Sakata et al., 2010
G215stop	mH_V1 [G211stop]	HEK wc	Yes							Sakata et al., 2010
I213stop	mH_V1 [I209stop]	HEK wc	Yes							Sakata et al., 2010
A210stop	mH_V1 [A206stop]	HEK wc	Yes			+V		H⁺	τ_act has weak V dependence	Sakata et al., 2010
L204stop	mH_V1 [L200stop]	HEK wc	No							Sakata et al., 2010

Mutant	Species	Expr. system	I?	τ_act	τ_tail	ΔV_thr	ΔpH slope	Selectivity	Other	Reference
E196C	CiH_V1 [A246C]	Xenopus TEVC	Yes						MTS_o open>closed	Gonzalez et al., 2010
L198C	CiH_V1 [I248C]	Xenopus TEVC	Yes						MTS_o open>closed	Gonzalez et al., 2010
G199C	CiH_V1 [G249C]	Xenopus i-o	Yes			2				Mony et al., 2015
L200W	CiH_V1 [L250W]	Xenopus TEVC	Yes	0.27	0.67					Okuda et al., 2016
L200W/ΔC	CiH_V1 [L250W/ΔC]	Xenopus TEVC	Yes	0.20	0.019					Okuda et al., 2016
I202C	CiH_V1 [V252C]	Xenopus TEVC	Yes						MTS_o open>closed	Gonzalez et al., 2010
R205A	hH_V1	HEK wc	Yes	0.0053	0.086	−1	48		0.63 × WT gating charge^a	Ramsey et al., 2006, 2010
R205A	hH_V1	Vesicle flux							Δ H⁺ flux^b	Letts, 2014
R205H^c/T222stop	hH_V1	COS wc	Yes					H⁺	Accessible to external Zn²⁺	Kulleperuma et al., 2013
R205Q	Mouse [R201Q]	HEK wc	Yes	Faster		−50			1.36 × WT gating charge^a	Sasaki et al., 2006
R205N	CiH_V1 [R255N]	Xenopus i-o	Yes						0.33 × WT gating charge^d	Gonzalez et al., 2013
R205N	CiH_V1 [R255N]	Xenopus TEVC	Yes			−36			0.78 × WT gating charge^a	Chamberlin et al., 2014
R205C	CiH_V1 [R255C]	Xenopus TEVC	Yes			−37			1.3 × WT gating charge^a	Chamberlin et al., 2014
R205A/R208A	hH_V1	HEK wc	Yes			128	51			Ramsey et al., 2010
R205A/R211A	hH_V1	HEK wc	Yes			96	45			Ramsey et al., 2010
L206C	CiH_V1 [L256C]	Xenopus TEVC	Yes						No MTS_o/i access	Gonzalez et al., 2010
W207A,^c W207S,^c or W207F^c	hH_V1	HEK/COS wc	Yes	0.01	0.034	−17.9	40	H⁺	Loss of selectivity at pH_o > 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	kH_V1 [W176A, W176S, W176F]	HEK/COS wc	Yes	0.025			40	H⁺		Cherny et al., 2015
W207A, W207S, or W207F	EhH_V1 [W278A, W278S, W278F]	HEK/COS wc	Yes	0.2		−28.2	50	H⁺		Cherny et al., 2015
W207I	CiH_V1 [W257I]	Xenopus TEVC	Yes	0.29	0.030					Okuda et al., 2016
W207I/A210A	CiH_V1 [W257I/F260A]	Xenopus TEVC	Yes	0.23	0.026					Okuda et al., 2016
R208A	hH_V1	HEK wc	Yes	0.0965	0.075	7	45			Ramsey et al., 2006, 2010
R208A	hH_V1	Vesicle flux							Δ H⁺ flux^b	Letts, 2014
R208A	hH_V1	Xenopus i-o	No							Hong et al., 2014
R208K	hH_V1	Xenopus i-o	Yes			−40			1.7 × WT gating charge^a	Hong et al., 2014
R208K	hH_V1	HEK/COS wc	Yes					H⁺		Dudev et al., 2015
R208H^c/T222stop	hH_V1	COS wc	Yes					H⁺	Accessible to external & maybe internal Zn²⁺	Kulleperuma et al., 2013
R208Q	hH_V1	Xenopus i-o	No							Hong et al., 2014
R208Q	Mouse [R204Q]	HEK wc	No							Sasaki et al., 2006
R208N	hH_V1	Xenopus i-o	No							Hong et al., 2014
R208N	CiH_V1 [R258N]	Xenopus i-o	Yes						0.50 × WT gating charge^d	Gonzalez et al., 2013
R208C	CiH_V1 [R258C]	Xenopus TEVC	Yes			−10			0.87 × WT gating charge^a	Chamberlin et al., 2014
V209C	CiH_V1 [V259C]	Xenopus TEVC	Yes						No MTS_o/i access	Gonzalez et al., 2010
R211A	hH_V1	HEK wc	Yes	2.24	0.092	70	53			Ramsey et al., 2006, 2010
R211A	hH_V1	Vesicle flux							Δ H⁺ flux^b	Letts, 2014
R211S	hH_V1	Xenopus i-o	Yes			35			0.72 × WT gating charge^a	Hong et al., 2014
R211S	hH_V1	Xenopus i-o	Yes			87	49	Gu⁺	at pH 8//8	Berger and Isacoff, 2011
R211S/I127C	CiH_V1 [R261S/I175C]	Xenopus i-o	Yes			15				Mony et al., 2015
R211H^c/T222stop	hH_V1	COS wc	Yes					H⁺	Accessible to internal Zn²⁺ when open	Kulleperuma et al., 2013
R211H/D112V/V116D^c	hH_V1	COS/HEK wc	Yes						Accessible to internal Zn²⁺ when open	Morgan et al., 2013
R211Q	mH_V1 [R207Q]	HEK wc	Yes			nc				Sasaki et al., 2006
R211N	CiH_V1 [R261N]	Xenopus i-o	Yes						0.38 × WT gating charge^d	Gonzalez et al., 2013
R211C	CiH_V1 [R261C]	Xenopus TEVC	Yes			54		H⁺	0.78 × WT gating charge^a	Chamberlin et al., 2014
R211C	NpHv1 [R163C]	HEK wc	Yes					H⁺		Chaves et al., 2016
I212C	CiH_V1 [I262C]	Xenopus TEVC	Yes						MTS_i closed>open	Gonzalez et al., 2010
N214K	hH_V1	HEK wc	Yes			−3	43		Inward rectification	Ramsey et al., 2010
N214R	hH_V1	HEK wc	Yes			10	40		Inward rectification	Ramsey et al., 2010
N214R	hH_V1	Xenopus i-o	No							Tombola et al., 2008
N214A	hH_V1	HEK wc	Yes			−3	42			Ramsey et al., 2010
N214A	hH_V1	Vesicle flux							nc H⁺ flux	Letts, 2014
N214R	mH_V1 [N210R]	HEK wc	Yes	Slow	Very slow	−V		H⁺		Sakata et al., 2010
N214D	hH_V1	COS/HEK wc	Yes					H⁺		Musset et al., 2011
N214C	CiH_V1 [N264C]	Xenopus TEVC	Yes						MTS_i closed>open	Gonzalez et al., 2010
G215A	hH_V1	COS/HEK wc	Yes		Fast			H⁺		Musset et al., 2011
I217stop	mH_V1 [I213stop]	HEK wc	Yes							Sakata et al., 2010
G215stop	mH_V1 [G211stop]	HEK wc	Yes							Sakata et al., 2010
I213stop	mH_V1 [I209stop]	HEK wc	Yes							Sakata et al., 2010
A210stop	mH_V1 [A206stop]	HEK wc	Yes			+V		H⁺	τ_act has weak V dependence	Sakata et al., 2010
L204stop	mH_V1 [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 hH_V1 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 ΔV_threshold value is the change in absolute position of the g_H–V relationship versus WT. The ΔpH slope is the slope in millivolts of the relationship between V_threshold (or other parameters reflecting the absolute position of the g_H–V relationship) and V_rev or E_H (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 (MTS_i or MTS_o, respectively) is listed as open>closed if the open channel was more accessible.

Slope factor of g_H–V relationship.

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

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

By limiting slope method.

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