Table 2.

Studies and characterization of ion channels by pharmacological inhibition or activation on human spermatozoa. AR, acrosomal reaction; AC, adenylate cyclase; sAC, soluble adenylate cyclase.

Ion Channel	Current	Inhibitor	Effect	Reference
hHv1	H+	hanatoxin-containing venom (Grammastola rosea)	No significant change in sperm hyperactivation A combination of venom and progesterone caused decreased full 360° rotation of the sperm flagella	Lishko et al., 2010 [102] Miller et al., 2018 [26]
		Corza6 (de novo peptide inhibitor)	AR inhibited by ∼70% No effect on sperm viability, sperm motility, or tyrosine phosphorylation pattern	Zhao et al., 2018 [103]
		Pantoprazole (proton-pump inhibitor)	Decreased sperm progressive motility and capacitation-induced sperm hyperactivation (hyperpolarization and protein phosphorylation)	Escoffier et al., 2020 [104]
CatSper1	Cations (Ca2+)	anti-CatSper1 IgG antibody (H-300)	Reduced sperm progressive motility after 1, 2, and 4 h of incubation Reduced sperm hyperactivated motility after 5 h of incubation	Li et al., 2009 [105]
CatSper		Ketamine	No effect on sperm viability, capacitation, or spontaneous AR Reduced intracellular calcium concentration	He et al., 2016 [106]
		NNC	Reduced sperm viability, motility, and velocity Inhibition of progesterone induced AR	Ghanbari et al., 2018 [107]
		Trequinsin hydrochloride	>hyperactivation and penetration into viscous medium <intracellular cGMP	McBrinn et al., 2019 [108]
CatSper and Hv1	Cations	NNC, ZnCl2, NNC + Zn	Reduced sperm viability, motility, and curvilinear velocity in all groups containing NNC, zinc, and NNC + zinc. The progesterone–induced acrosome reaction was abolished by each of these inhibitors. The combinatory effect of NNC plus zinc on motility and progesterone–induced acrosome reaction was no stronger than NNC by itself.	Keshtgar et al., 2018 [109]
CatSper and hSLO3	Cations	RU1968	Reduced progesterone-induced sperm hypermotility Minor inhibitory effect on hSLO3 rather than CatSper	Rennhack et al., 2018 [110]
TRPV1	Cations	Capsazepine	Inhibition of progesterone-promoted sperm-oocyte fusion Reduced progesterone-induced AR rate, reduced spontaneous AR rate No effect on sperm motility	Francavilla et al., 2009 [111]
ENaC	Na+	EIPA	Improved sperm motility in healthy donors and asthenozoospermic patients	Kong et al., 2009 [112]
NaV	Na+	Lidocaine	Induction of hyperactivated motility	Candenas et al., 2018 [113]
NHE1/SLC9A1	Na+/H+	EIPA	No effect on AR	Garcia and Meizel, 1999 [114]
NBC	Na+/HCO3−	S0859	Lower PKA activity	Puga Molina et al., 2018 [115]
NCX	Na+/Ca2+	bepridil, DCB, KB-R7943	Impaired sperm motility	Krasznai et al., 2006 [116]
CFTR	Anions (Cl−)	CFTRinh-172	Inhibition of progesterone-induced sperm capacitation, cAMP synthesis, hyperactivated motility, and rhuZP3a-induced AR	Li et al., 2010 [117]
Cl− channels	Cl−	Adjudin (Cl− channels blocker)	Reduced sperm hyperactivation but no effect on sperm motility Blockage of rhuZP3b- and progesterone-induced AR in a dose-dependent manner Inhibition of forskolin-activated transmembrane AC and sAC activity Impaired serine and threonine sperm protein phosphorylation Prevention of sperm penetration of zona-free hamster eggs	Li et al., 2013 [118]
TMEM16A/ANO1	Cl−	NFA, DIDS, TMEM16Ainh	Reduced rhZP3-induced AR	Orta et al., 2012 [119]
K channels	K+	Quinine	Increased sperm volume, reduced sperm kinematics and mucus penetration K-ionophores valinomycin and gramicidin counteract 4-aminopyridine but not TEA (K-blockers) Can mimic quinine	Yeung and Cooper, 2001 [120]
hSLO3	K+	Progesterone, Ba2þ and Quinidine (+++) Penitrem A and Charybdotoxin (+) Iberiotoxin and Slotoxin (~)	Pharmacological comparison of the CAH and hSlo3 profiles indicates that in addition to hSlo3, other K+ channels (possibly Slo1) may participate in CAH	Sanchez-Carranza et al., 2015 [121]
NaV	Na+	Veratridine	>sperm progressive motility without producing hyperactivation >protein tyrosine phosphorylation Blockage of progesterone-induced AR Membrane depolarisation	Candenas et al., 2018 [113]