title: Niflumic acid disrupts marine spermatozoan chemotaxis without impairing the spatiotemporal detection of chemoattractant gradients.
abstract: In many broadcast-spawning marine organisms, oocytes release chemicals that guide conspecific spermatozoa towards them through chemotaxis. In the sea urchin Lytechinus pictus, the chemoattractant peptide speract triggers a train of fluctuations of intracellular Ca(2+) concentration in the sperm flagella. Each transient Ca(2+) elevation leads to a momentary increase in flagellar bending asymmetry, known as a chemotactic turn. Furthermore, chemotaxis requires a precise spatiotemporal coordination between the Ca(2+)-dependent turns and the form of chemoattractant gradient. Spermatozoa that perform Ca(2+)-dependent turns while swimming down the chemoattractant gradient, and conversely suppress turning events while swimming up the gradient, successfully approach the center of the gradient. Previous experiments in Strongylocentrotus purpuratus sea urchin spermatozoa showed that niflumic acid (NFA), an inhibitor of several ion channels, drastically altered the speract-induced Ca(2+) fluctuations and swimming patterns. In this study, mathematical modeling of the speract-dependent Ca(2+) signaling pathway suggests that NFA, by potentially affecting hyperpolarization-activated and cyclic nucleotide-gated channels, Ca(2+)-regulated Cl(-) channels and/or Ca(2+)-regulated K(+) channels, may alter the temporal organization of Ca(2+) fluctuations, and therefore disrupt chemotaxis. We used a novel automated method for analyzing sperm behavior and we identified that NFA does indeed disrupt chemotactic responses of L. pictus spermatozoa, although the temporal coordination between the Ca(2+)-dependent turns and the form of chemoattractant gradient is unaltered. Instead, NFA disrupts sperm chemotaxis by altering the arc length traveled during each chemotactic turning event. This alteration in the chemotactic turn trajectory disorientates spermatozoa at the termination of the turning event. We conclude that NFA disrupts chemotaxis without affecting how the spermatozoa decode environmental cues.
authors: Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, 62210, México.
authors: Adán
authors: A
authors: Guerrero
authors: Jesús
authors: J
authors: Espinal
authors: Christopher D
authors: CD
authors: Wood
authors: Juan M
authors: JM
authors: Rendón
authors: Jorge
authors: J
authors: Carneiro
authors: Gustavo
authors: G
authors: Martínez-Mekler
authors: Alberto
authors: A
authors: Darszon
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D005407:Flagella / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008297:Male; D009544:Niflumic Acid / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D012617:Sea Urchins; D015398:Signal Transduction; D013083:Sperm Transport / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology
chemical_list: D007473:Ion Channels; D009842:Oligopeptides; D009544:Niflumic Acid; C028364:speract
keywords: Ca2+ signaling; Chemotaxis; Niflumic acid; Sperm