Discrete Dynamics Model for the Speract-Activated Ca2+ Signaling Network Relevant to Sperm Motility

Abstract

Understanding how spermatozoa approach the egg is a central biological issue. Recently a considerable amount of experimental evidence has accumulated on the relation between oscillations in intracellular calcium ion concentration ([Ca]) in the sea urchin sperm flagellum, triggered by peptides secreted from the egg, and sperm motility. Determination of the structure and dynamics of the signaling pathway leading to these oscillations is a fundamental problem. However, a biochemically based formulation for the comprehension of the molecular mechanisms operating in the axoneme as a response to external stimulus is still lacking. Based on experiments on the S. purpuratus sea urchin spermatozoa, we propose a signaling network model where nodes are discrete variables corresponding to the pathway elements and the signal transmission takes place at discrete time intervals according to logical rules. The validity of this model is corroborated by reproducing previous empirically determined signaling features. Prompted by the model predictions we performed experiments which identified novel characteristics of the signaling pathway. We uncovered the role of a high voltage-activated channel as a regulator of the delay in the onset of fluctuations after activation of the signaling cascade. This delay time has recently been shown to be an important regulatory factor for sea urchin sperm reorientation. Another finding is the participation of a voltage-dependent calcium-activated channel in the determination of the period of the fluctuations. Furthermore, by analyzing the spread of network perturbations we find that it operates in a dynamically critical regime. Our work demonstrates that a coarse-grained approach to the dynamics of the signaling pathway is capable of revealing regulatory sperm navigation elements and provides insight, in terms of criticality, on the concurrence of the high robustness and adaptability that the reproduction processes are predicted to have developed throughout evolution.

Niflumic acid disrupts marine spermatozoan chemotaxis without impairing the spatiotemporal detection of chemoattractant gradients

“…Furthermore, we recently found that the highly specific blocker of CaKC Iberiotoxin at 100 nM increases the period between the [Ca 2+ ] i fluctuations triggered by speract in S. purpuratus spermatozoa (Espinal et al, 2011). If CaCC and/or CaKC channels participate in the speract signaling pathway, they would open in response to Ca 2+ entry, leading to influx of Cl 2 and/or efflux of K + , and therefore V m hyperpolarization (Fig.…”

“…In a previous work (Espinal et al, 2011), we developed a discrete logical model to describe the temporal dynamics of the speract-activated signaling network in the S. purpuratus sea urchin sperm flagellum. Encouraged by the experimental validation of the model predictions (Espinal et al, 2011), here we used this model to investigate in silico the effect on the [Ca 2+ ] i oscillations of altering the NFAsensitive channels present in the sea urchin sperm flagellum.…”

“…Encouraged by the experimental validation of the model predictions (Espinal et al, 2011), here we used this model to investigate in silico the effect on the [Ca 2+ ] i oscillations of altering the NFAsensitive channels present in the sea urchin sperm flagellum. The model consists of 22 nodes representing the principal components involved, or likely participating, in the signaling cascade: ion channel activities, intracellular ion and molecular concentrations and the membrane potential, amongst others.…”

“…This fast transient increase in flagellar [Ca 2+ ] i has been associated with the transient increases in flagellar bending that prompt sea urchin spermatozoa to undergo a turning event. It has been proposed that the [Ca 2+ ] i increases could lead to the opening of Ca 2+ -regulated Cl 2 channels (CaCC) and/or Ca 2+ -regulated K + channels (CaKC), which would then contribute to hyperpolarize the V m again, removing inactivation from CaV channels and opening HCN channels (Wood et al, 2007;Espinal et al, 2011). It is thought that this series of events is then cyclically repeated generating a sequence of V m -dependent turns.…”

“…In a companion article (J.E., A.D., A.G. and G.M.-M., unpublished) we investigated how NFA could modify the Ca 2+ fluctuation dynamics using a logical network model for the speract-activated Ca 2+ signaling pathway developed by Espinal et al (Espinal et al, 2011). Here, based on the results of this model under conditions in which it can reproduce the experimental findings of Wood et al (Wood et al, 2003;Wood et al, 2007), we anticipate that in the presence of speract gradients, [Ca 2+ ]i fluctuations would no longer be biased towards the descending gradients in the presence of NFA.…”