comparison between inhibition of catsper and ksper channels with nnc 55-0396 and quinidine on human sperm function

Background: calcium enters human sperm through the “cation channel of sperm” (catsper), while potassium ions exit via the sperm potassium channel (ksper). these two channels regulate intracellular calcium concentration ([ca2+]i) and membrane potential. our study aims to investigate and compare the contributions of these channels in capacitated sperm function. methods: this study was conducted at the physiology department of shiraz medical school in 2022. thirty-six semen samples were washed, and the supernatants were discarded. then, 0.5 ml of modified-supplemented earle’s balanced salt solution (m-sebss) was added to the sediments. samples were incubated at 37 ̊c and 5% co2. the motile spermatozoa were aspirated after swimming up, and the samples were diluted with m-sebss to 10×106 spermatozoa per ml. the samples were divided into four groups: control, solvent (dimethyl-sulphoxide (dmso), nnc55-0396 (nnc) (10 μm), and quinidine (100 μm) as catsper and ksper blockers, respectively. sperm kinematics were evaluated by a computer-assisted sperm analyzer. the samples were stained with eosin-y and fitc-psa to assess sperm viability and acrosomal reaction. the [ca2+]i was examined by flow cytometry using fluo-3am. the parametric and non-parametric data were analyzed using one-way anova and kruskal-wallis test.results: nnc and quinidine significantly decreased progressive sperm motility (p=0.001) and reduced sperm kinematics (p=0.001). nnc but not quinidine significantly decreased sperm survival (p=0.001), reduced [ca2+]i in live spermatozoa (p=0.05), and induced the acrosomal reaction (p=0.012). conclusion: inhibition of ksper without effect on [ca2+]i can inhibit sperm motility and increase mortality rate. it seems that the function of ksper is as vital as catsper in human sperm physiology.