Table 4. Changes in H V 1 properties in... | Rockefeller University Press

Table 4.

Changes in H_V1 properties in S2 (134–156) and S2–S3 linker (157–165) mutants versus WT channels

Mutant	Species	Expr. system	I?	ΔV_thr	ΔpH slope	Selectivity	Other	Reference
Y134A	hH_V1	HEK wc	Yes	3				Ramsey et al., 2010
H140A	hH_V1	HEK wc	Yes			H⁺	9 × K_d^{^a} Zn²⁺	Ramsey et al., 2006
H140A	hH_V1	Vesicle flux					nc H⁺ flux	Letts, 2014
H193A	hH_V1	HEK wc	Yes			H⁺	39 × K_d^{^a} Zn²⁺	Ramsey et al., 2006
H140A/ H193A	hH_V1	HEK wc	Yes	−12	46	H⁺	2,000 × K_d^{^a} Zn²⁺	Ramsey et al., 2006
H140A/ H193A	hH_V1	COS/HEK wc	Yes			H⁺		Musset et al., 2011
Y141A	hH_V1	HEK wc	Yes	−27				Ramsey et al., 2010
S143A	hH_V1	HEK wc	Yes	11	41			Ramsey et al., 2010
S143A	hH_V1	Vesicle flux					nc H⁺ flux	Letts, 2014
D112V/S143D	hH_V1	COS/HEK wc	Yes			Cl^–		Morgan et al., 2013
D112V/I146D	hH_V1	COS/HEK wc	No					Morgan et al., 2013
D112V/L147D	hH_V1	COS/HEK wc	No					Morgan et al., 2013
F150A	hH_V1	Xenopus i-o	Yes	−24				Hong et al., 2013
F150C	hH_V1	Xenopus i-o	Yes	−22				Hong et al., 2013
F150W	hH_V1	Xenopus i-o	Yes	−55				Hong et al., 2013
E153A	hH_V1	HEK wc	Yes	−55	42			Ramsey et al., 2010
E153A	CiH_V1 [E201A]	Xenopus TEVC	No					Chamberlin et al., 2014
E153G	CiH_V1 [E201G]	Xenopus TEVC	No					Chamberlin et al., 2014
E153N	hH_V1	HEK wc	Yes	−1.17	45			Ramsey et al., 2010
E153A	hH_V1	Vesicle flux					nc H⁺ flux	Letts, 2014
E153D	hH_V1	HEK wc	Yes	−23	37			Ramsey et al., 2010
E153D/D174E	hH_V1	HEK wc	Yes	−102	40			Ramsey et al., 2010
E153C	hH_V1	Xenopus i-o	Yes	−55				Tombola et al., 2010
E153C	CiH_V1 [E201C]	Xenopus TEVC	Yes	−101				Chamberlin et al., 2014
E153C/R205C	CiH_V1 [E201C/R255C]	Xenopus TEVC	Yes	−43				Chamberlin et al., 2014
E153C/R208	CiH_V1 [E201C/R258C]	Xenopus TEVC	Yes	37				Chamberlin et al., 2014
E153C/R211C	CiH_V1 [E201CR261C]	Xenopus TEVC	Yes	−60				Chamberlin et al., 2014
K157A	hH_V1	HEK wc	Yes	1	39			Ramsey et al., 2010
K157A	hH_V1	Vesicle flux					nc H⁺ flux	Letts, 2014
R162A	hH_V1	HEK wc	Yes	13				Ramsey et al., 2010

Mutant	Species	Expr. system	I?	ΔV_thr	ΔpH slope	Selectivity	Other	Reference
Y134A	hH_V1	HEK wc	Yes	3				Ramsey et al., 2010
H140A	hH_V1	HEK wc	Yes			H⁺	9 × K_d^{^a} Zn²⁺	Ramsey et al., 2006
H140A	hH_V1	Vesicle flux					nc H⁺ flux	Letts, 2014
H193A	hH_V1	HEK wc	Yes			H⁺	39 × K_d^{^a} Zn²⁺	Ramsey et al., 2006
H140A/ H193A	hH_V1	HEK wc	Yes	−12	46	H⁺	2,000 × K_d^{^a} Zn²⁺	Ramsey et al., 2006
H140A/ H193A	hH_V1	COS/HEK wc	Yes			H⁺		Musset et al., 2011
Y141A	hH_V1	HEK wc	Yes	−27				Ramsey et al., 2010
S143A	hH_V1	HEK wc	Yes	11	41			Ramsey et al., 2010
S143A	hH_V1	Vesicle flux					nc H⁺ flux	Letts, 2014
D112V/S143D	hH_V1	COS/HEK wc	Yes			Cl^–		Morgan et al., 2013
D112V/I146D	hH_V1	COS/HEK wc	No					Morgan et al., 2013
D112V/L147D	hH_V1	COS/HEK wc	No					Morgan et al., 2013
F150A	hH_V1	Xenopus i-o	Yes	−24				Hong et al., 2013
F150C	hH_V1	Xenopus i-o	Yes	−22				Hong et al., 2013
F150W	hH_V1	Xenopus i-o	Yes	−55				Hong et al., 2013
E153A	hH_V1	HEK wc	Yes	−55	42			Ramsey et al., 2010
E153A	CiH_V1 [E201A]	Xenopus TEVC	No					Chamberlin et al., 2014
E153G	CiH_V1 [E201G]	Xenopus TEVC	No					Chamberlin et al., 2014
E153N	hH_V1	HEK wc	Yes	−1.17	45			Ramsey et al., 2010
E153A	hH_V1	Vesicle flux					nc H⁺ flux	Letts, 2014
E153D	hH_V1	HEK wc	Yes	−23	37			Ramsey et al., 2010
E153D/D174E	hH_V1	HEK wc	Yes	−102	40			Ramsey et al., 2010
E153C	hH_V1	Xenopus i-o	Yes	−55				Tombola et al., 2010
E153C	CiH_V1 [E201C]	Xenopus TEVC	Yes	−101				Chamberlin et al., 2014
E153C/R205C	CiH_V1 [E201C/R255C]	Xenopus TEVC	Yes	−43				Chamberlin et al., 2014
E153C/R208	CiH_V1 [E201C/R258C]	Xenopus TEVC	Yes	37				Chamberlin et al., 2014
E153C/R211C	CiH_V1 [E201CR261C]	Xenopus TEVC	Yes	−60				Chamberlin et al., 2014
K157A	hH_V1	HEK wc	Yes	1	39			Ramsey et al., 2010
K157A	hH_V1	Vesicle flux					nc H⁺ flux	Letts, 2014
R162A	hH_V1	HEK wc	Yes	13				Ramsey 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. 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).

Nominal K_d values are nearly meaningless for Zn²⁺ inhibition of H_V1 because its main effects are slowing activation and shifting the g_H–V relationship positively (Cherny and DeCoursey, 1999). As demonstrated in the Appendix of DeCoursey et al. (2001a), the apparent K_d derived from the ratio I_H(Zn²⁺)/I_H can vary more than three orders of magnitude depending on the test potential selected. If all measurements are done the same way, relative K_d values have meaning.

[ViewLarge]