Table 2.

A summary of nematode GluCl subunits and receptor pharmacology.

Organism	GluCl gene	Subunit	Tissue distribution	Receptor	Pharmacology
					Glutamate (EC50)	IVM (EC50)	PTX (IC50)
C. elegans	glc-1	GLC-1 (GluClα1)	intestine, pharyngeal and body wall muscle, head neurons1	Expresses as IVM-gated homomeric channel2	No response2	140 nM2	59 μM3 for IVM sensitive current
	glc-2	GLC-2 (GluClβ)	Pm4 pharyngeal muscle cell4	Forms a glutamate sensitive homomeric channel2	380 μM2	No response2	77 nM3 for glutamate-sensitive current
				GLC-1 and GLC-2 assemble to form heteromeric channels2	1.36 mM2	190 nM2	42 μM for glutamate-sensitive current and 52 μM for IVM-sensitive current3
	glc-3	GLC-3/ GluClα4	AIY interneurons5,6	Expresses as glutamate-gated homomeric channels7	1.9 mM7	0.4 μM7	PTX (0.01–1000 μm) failed to inhibit the L-glutamate (3 mM) agonist response7
	glc-4	GLC-4A (full length variant) GLC-4B (truncated variant)	intestine, AIY interneurons, anal depressor muscle, head mesodermal cell, nerve ring, head and tail neurons8,9	GLC-4A failed to form a functional homomeric channel8	No response	No response	Not determined
	avr-14	AVR-14A/ GluClα3A	neurons in ring ganglion, ventral cord, and mechanosensory neurons10	AVR-14A failed to show functional channel expression10	No response	No response	Not determined
		AVR-14B/ GluClα3B	neurons in ring ganglion, ventral cord, and mechanosensory neurons10	AVR-14B expresses as functional homomeric channels10	Robust response to 10 mM glutamate10	Robust response to 10 μM IVM10	Not determined
				AVR-14B forms a heteromeric receptor with GLC-4A8	∼21 fold reduction in 1 mM glutamate current amplitude8	∼19 fold reduction in 10 μM IVM current amplitude8	Not determined
	avr-15	AVR-15A/ GluClα2A	pharyngeal muscle (pm4 and 5), head neurons, sublateral nerve cords and mechanosensory neurons11	AVR-15A forms a homomeric receptors11	2 mM11	Robust response to 10 μM IVM11	Not determined
		AVR-15B/ GluClα2B	pharyngeal muscle (pm4 and 5), head neurons, sublateral nerve cords and mechanosensory neurons11	AVR-15B forms a homomeric receptors12	208.3 μM12	107.8 nM12	Weak inhibition of glutamate-mediated currents by 100 PTX μM12
				AVR-15B assembles into a heteromeric receptors with GLC-212	62 μM12	103 nM12	Not determined
H. contortus	GluClα	GluClαA/ GLC-5A	Motor neuron commissures13	GLC-5A forms a functional homomeric receptors14	8.4 μM14	131 nM14	weak inhibition of IVM and moxidectin induced currents by 100 PTX μM14
		GluClαB/ GLC-5B	Motor neuron commissures13	Not determined	Not determined	Not determined	Not determined
	glc-2/ HG4	GLC-2 (GluClβ)	Motor neuron commisures, lateral and subventral nerve cords13,15	GLC-2 forms a homomeric receptors16	394 μM16	>10 μM16	Not determined
	avr-14/ gbr-2/ GluClα3	AVR-14A/ GluClα3A	amphidial neurons, motor neuron commissures, lateral and ventral nerve cords, and nerve ring13,17	No functional homomeric channels have been reported for AVR-14A	No response	No response	No response
		AVR-14B/ GluClα3B	pharyngeal neurons, amphidial neurons, motor neuron commissures, lateral and ventral nerve cords, and nerve ring13,17,18	AVR-14B forms a homomeric receptors16	15.3 μM19 28 μM16 27.6 μM20	39 nM19 22 nM16 ∼0.1 ± 1.0 nM20	1 mM PTX was a potent blocking of glutamate- and IVM- current response20
				AVR-14B forms a heteromeric channel when co-injected with GLC-5A in the ratio of 1:1 or 1:5016	40 μM (1:1) 16 44 μM (1:50)16	86 nM (1:1) 16 141 nM (1:50)16	Not determined
	glc-3	GLC-3/ GluClα4	Not known	Not characterized	Not determined
	glc-4	GLC-4	Not known	Not characterized	Not determined
	glc-6	GLC-6	Not known	Not characterized	Hco-GLC-6 subunit rescues the ivermectin sensitivity of the C. elegans DA1316 triple GluCl mutant (avr-14, avr-15, glc-1) strain. This suggests that GLC-6 subunit likely expresses an IVM-sensitive channel either alone or in combination with other subunits21
D. immits	avr-14	AVR-14A/ GluClα3	Not known	No functional homomeric channels have been reported for AVR-14A	No response	No response	No response
		AVR-14B/ GluClα3B	Not known	AVR-14B expresses as a functional homomeric channel22	l-glutamate sensitive channel (1–100 mM) 22	1 μM IVM produced saturating currents22	Not determined
C. oncophora	GluClβ from ivermectin sensitive (IVS) and ivermectin resistant (IVR) worms	IVS GluClβ/ GLC-2	Not known	IVS GLC-2 expresses as a homomeric channel	185.6 μM	No response	Not determined
		IVR GluClβ/ GLC-2	Not known	No functional homomeric channel have been reported from IVR GLC-2	No response	No response	Not determined
	IVS and IVR GluClα3	IVS AVR-14/ GluClα3	Not known	IVS AVR-14 expresses as a homomeric channel23	29.7 μM23	0.5 μM23	Not determined
				IVS AVR-14/GluClβ express as heteromeric channels23	13.4 μM23	Not determined	Not determined
		IVR AVR-14/ GluClα3	Not known	IVR AVR-14 expresses as a homomeric channel23	96.1 μM23	1.3 μM23	Not determined
				IVR AVR-14/GluClβ express as heteromeric channels23	171.6 μM23	Not determined	Not determined
A. suum	GluCla3	AVR-14/ GluCla3	Dorsal and ventral nerve cord17	Not characterized	Not determined	Not determined	Not determined
B. malayi	GluCla3	AVR14A/ GluCla3A AVR14B/ GluCla3B	tissues surrounding ES apparatus, the inner body, and anal pore, reproductive tissue24, 25	Not characterized	Not determined	Not determined	Not determined

¹Ghosh et al. (2012).

²Cully et al. (1994).

³Etter et al. (1999).

⁴Laughton et al. (1997b).

⁵Wenick and Hobert (2004).

⁶Chalasani et al. (2007).

⁷Horoszok et al. (2001).

⁸Pellegrino (2003).

⁹Wang et al. (2021).

¹⁰Dent et al. (2000).

¹¹Dent et al. (1997).

¹²Vassilatis et al. (1997a).

¹³Portillo et al. (2003).

¹⁴Forrester et al. (2003).

¹⁵Delany et al. (1998).

¹⁶Atif et al. (2019).

¹⁷Jagannathan et al. (1999).

¹⁸Yates et al. (2003).

¹⁹Lynagh and Lynch (2010).

²⁰McCavera et al. (2009).

²¹Glendinning et al. (2011).

²²Yates and Wolstenholme (2004).

²³Njue et al. (2004).

²⁴Li et al. (2014b).

²⁵Moreno et al. (2010).