TABLE 1.

Summary of σ1R activation effects on VGICs.

Functional effects on currents∗	Mode of activation	Experimental system	Mechanism/Evidence	References
Ca2+ currents
↓N, L, P/Q and R-type	Haloperidol, ibogaine, (+)-pentazocine, DTG	Parasympathic intracardiac neurons; superior cervical ganglia (cell culture)	Direct/2nd messenger systems and G proteins not required	Zhang and Cuevas, 2002∗∗
↓L-type	(+)-SKF10047	Retinal ganglion cells (cell culture)	Direct/co-IP	Tchedre et al., 2008
Na+ currents
↓Nav1.5	(+)-pentazocine, (+)-SKF10047	Cell lines (HEK293, COS-7), Cardiac myocytes	Direct/2nd messenger systems and G proteins not required	Johannessen et al., 2009; Fontanilla et al., 2009
	None	tsA 201 cells, breast cancer cell lines (MDA-MB-231)	AFM	Balasuriya et al., 2012
	(+)-pentazocine	intracardiac ganglion neurons (isolated neurons from neonatal rats)	nd	Zhang et al., 2009
K+ currents
↓IA	Pentazocine, SKF10047	Neurohypophysial terminals (pituitary gland slices)	Direct/2nd messenger systems and G proteins not required	Lupardus et al., 2000
	JO 1784, (+)-pentazocine	Neuroendocrine pituitary cell culture	Indirect/Gs protein required	Soriani et al., 1999a
↓IA (Kv1.4)	SKF10047	Xenopus oocytes; rat posterior pituitary gland	Direct/co-IP	Aydar et al., 2002
↓IK(DR), IBK	DTG, (+)-pentazocine, ibogaine,	Parasympathic intracardiac neurons (cell culture), neuroendocrine pituitary cell culture	Direct/2nd messenger systems and G proteins not required	Soriani et al., 1998; Zhang and Cuevas, 2005
↓IM	(+)-pentazocine	Primary frog neuroendocrine pituitary cell culture	Indirect/Gs protein required	Soriani et al., 1999b
↑Kv1.2	In vitro and in vivo cocaine	Brain tissue (NAc and PFC); cell lines (NG108-15, Neuro2A, HEK293T)	Direct/co-IP	Kourrich et al., 2013; Delint-Ramirez et al., 2018
↓Kv1.3	±σ1R expression	Xenopus oocytes; HEK 293 cells	Direct/co-IP	Kinoshita et al., 2012
	(+)-pentazocine, igmesine, DTG	Jurkat cells	nd	Renaudo et al., 2004
↓Kv1.5	SKF10047	Xenopus oocytes	G protein-independent	Aydar et al., 2002
↑Kv2.1	Cyproheptadine, PRE-084	Mouse cortical neurons, HEK293T cells	Gi protein-dependent	He et al., 2012
↓IhERG (Kv11.1)	Igmesine	Xenopus oocytes; HEK293; human K562; myeloid leukemia cells	Direct/co-IP	Crottès et al., 2011
	none	HCT116 human; colorectal cancer cells	Direct/FRET/Proximity Ligation Assay	Balasuriya et al., 2014
		HEK293	Direct/FRET, AFM
↓Kir2.1	SKF10047	Mouse embryonic fibroblasts	nd	Wong et al., 2016

^∗All effects on ion channels’ current were obtained with electrophysiological recordings. ^∗∗Rank order potency of various σR ligands suggest these effects may be through σ2R. AFM, atomic force microscopy; co-IP, coimmunoprecipitation; I_A, A-type K⁺ current; I_BK, large-conductance Ca^{2 +}-activated K⁺ current; I_hERG, human ether-à-gogo K⁺ current; I_K(DR), delayed outwardly rectifying K⁺ current; NAc, nucleus accumbens; nd, not determined; PFC, prefrontal cortex.