Table 2.

Effects of bile acids on ion channels and ionotropic receptors

Ion Channel	Bile Acid	Effect: Stimulation ↑ Inhibition ↓	Concentration Used or EC50/IC50, if Available	Solvent	Cells Expression System	Refs.
Epithelial sodium channel/degenerin ion channel family
BASICrat	g-CDCA, t-CDCA g-HDCA, t-HDCA	↑↑↑	1–1.5 mM g-HDCA: EC50 ∼ 2 mM	NA	X. laevis oocytes	(77, 78)
	t-CA, t-βMCA	↑
	UDCA	↑↑↑	EC50 ∼ 2.5 mM
	t-UDCA, t-HDCA	↑↑↑	1–2 mM t-UDCA: EC50 ∼ 2.7 mM	NA	HEK293 cells	(79)
	t-CA, t-LCA t-DCA, t-CDCA	↑↑
	t-CDCA, t-HDCA t-UDCA	↑↑	500 µM–1 mM	NA	Normal rat cholangiocytes (NRC)	(80)
BASIChuman	t-DCA	↑↑↑	500 µM–1 mM	Bath solution	X. laevis oocytes	(77, 81, 82)
	t-CDCA	↑↑↑		NA
	t-CA, t-HDCA	↑
	t-DCA, t-CDCA	↑↑↑	1–2 mM	NA	HEK293 cells	(79)
	t-CA, t-UDCA t-HDCA, t-LCA	↑
BASICmouse	t-CA, t-UDCA, t-HDCA t-LCA, t-DCA, t-CDCA	↑↑	1–2 mM t-UDCA: EC50 ∼ 4.5 mM	NA	HEK293 cells	(79)
αβγENaCrat	CA	↑↑	1 mM t-DCA: EC50 ∼ 260 µM t-CA: EC50 ∼ 410 µM	DMSO stock	X. laevis oocytes	(83)
	t-DCA	↑↑↑		Bath solution
	g-CA, t-CA	↑↑
	t-CDCA, t-UDCA	↑
	t-βMCA, t-HDCA	No effect
αβγENaChuman	t-DCA	↑↑↑	250 µM	Bath solution	X. laevis oocytes	(84)
	t-CA, t-CDCA	↑↑
	CA, DCA	↑
	CDCA	↓
δβγENaChuman	CA, t-CA, DCA, t-DCA CDCA, t-CDCA	↑↑↑
αβγENaCmouse	DCA, t-CA	↑↑↑	1 mM DCA: EC50 ∼ 80 µM t-CA: EC50 ∼ 150 µM	H2O stock	X. laevis oocytes	(85)
	g-CA	↑↑
	CA, t-LCA, UCA	↑↑		DMSO stock
	CDCA, t-CDCA 12βHICA	↑
	HDCA	↓		H2O stock
	t-HDCA	↓↓
	t-CA	↑↑	1 mM t-CA: EC50 ∼ 200 µM	H2O stock	mpkCCD14 cells
	t-HDCA	↓
ENaChuman	UDCA	↓↓	500 µM	NA	NuLi-1 and CuFi-1 airway epithelial cells	(86)
ASIC1ahuman	t-CDCA	↑↑↑	500 µM t-DCA: EC50 ∼ 150 µM	Bath solution	X. laevis oocytes	(87)
	t-DCA	↑↑
	t-CA	↑
Other ion channels and ionotropic receptors
BKCarabbit	CA, DCA, LCA, t-LCA	↑↑↑	100 µM	DMSO ethanol stock	Smooth muscle cells	(88)
NMDAmouse	CA, g-CA, t-CA	↓↓↓	IC50 ∼ 500-700 µM	NA	Hypothalamic neurons	(89, 90)
	DCA, t-DCA CDCA, t-CDCA		IC50 ∼ 60-70 µM
	g-CDCA		IC50 ∼ 130 µM
GABAAmouse	CA, g-CA, t-CA	↓↓↓	IC50 ∼ 500–700 µM
	DCA, t-DCA		IC50 ∼ 150 µM
	CDCA, g-CDCA t-CDCA		IC50 ∼ 70–80 µM
	UDCA		IC50 ∼ 70–100 µM
GABAA α1ratβ1ratγ2Lmouse α1ratβ2ratγ2Lmouse α1ratβ3humanγ2Lmouse α1ratβ3human	UDCA	↓↓↓	IC50 ∼ 70–100 µM	NA	HEK293 cells	(90)
β3human β3humanγ2Lmouse			IC50 ∼ 7 µM IC50 ∼ 200 µM
NMDA GluN1rat/2Arat GluN1rat/2Brat	CA, g-CA, t-CA CDCA, g-CDCA t-CDCA	↓	100 µM	NA	X. laevis oocytes	(91)
GluN1rat/2Drat	CA, g-CA, t-CA	↓	100 µM t-CDCA: IC50 ∼ 180 µM
	CDCA, g-CDCA t-CDCA	↓↓
GluN1rat/3Bmouse	CA, g-CA, t-CA	↓	100 µM t-CDCA: IC50 ∼ 40–80 µM
	CDCA, g-CDCA t-CDCA	↓↓↓
P2X4human	CA, t-CA, CDCA	No effect	250–500 µM t-DCA: IC50 ∼ 160 µM	Bath solution	X. laevis oocytes	(92)
	t-CDCA	↓↓
	DCA, t-DCA	↓↓↓
P2X2rat	t-CA	No effect	20 µM t-HDCA: IC50 ∼ 11 µM	H2O stock	X. laevis oocytes	(93)
	t-UDCA, t-DCA	↓
	t-CDCA	↓↓
	t-LCA, HDCA t-HDCA, g-HDCA	↓↓↓
P2X1rat	t-HDCA	No effect	20 µM
	t-LCA	↓	200 µM
P2X3rat	t-HDCA	No effect	20 µM
P2X7rat	t-LCA		200 µM
P2X4rat	t-LCA	↑	200 µM
	t-HDCA	No effect	20 µM
P2X2human	t-LCA	↑↑	20 µM
	t-HDCA	No effect

CA, cholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; HDCA, hyodeoxycholic acid; LCA, lithocholic acid; UCA, ursocholic acid; UDCA, ursodeoxycholic acid; 12βHICA, 12β-hydroxyisocholic acid; βMCA, β-muricholic acid; t-, tauro-conjugated; g-, glyco-conjugated bile acid. Solvents: NA, no information available; bath solution, bile acids/bile salts were directly dissolved in bath solution to obtain the indicated final concentrations; DMSO stock, dimethyl sulfoxide (DMSO) stock solutions were prepared with bile acids at a concentration of 100 mM; H₂O stock, aqueous stock solutions were prepared with bile acid concentrations ranging from 20 to 100 mM; DMSO/ethanol stock, concentrated dimethyl sulfoxide (DMSO) stock solutions were prepared with bile acids at a concentration of 333 mM and then further diluted 1/10 in 95% ethanol.