Biology subjects

Trevino, C. L.

Publications and source records attributed to Trevino, C. L..

3 recordsLinked to original sources

bioRxiv2024

The sodium-proton exchangers sNHE and NHE1 control plasma membrane hyperpolarization in mouse sperm.

Sperm capacitation, crucial for fertilization, occurs in the female reproductive tract and can be replicated in vitro using a medium rich in bicarbonate, calcium, and albumin. These components trigger the cAMP-PKA signaling cascade, proposed to promote hyperpolarization of the mouse sperm plasma membrane through activation of SLO3 K+ channel. Hyperpolarization is a hallmark of capacitation: proper membrane hyperpolarization renders higher in vitro fertilizing ability, while Slo3 KO mice are infertile. However, the precise regulation of SLO3 opening remains elusive. Our study challenges the involvement of PKA in this event and reveals the role of Na+/H+ exchangers. During capacitation, calcium increase through CatSper channels activates NHE1, while cAMP directly stimulates the sperm-specific NHE, collectively promoting the alkalinization threshold needed for SLO3 opening. Hyperpolarization then feeds back Na+/H+ activity. Our work is supported by pharmacology, and a plethora of KO mouse models, and proposes a novel pathway leading to hyperpolarization. TeaserAlkalinization of sperm cytoplasm activates potassium channels to hyperpolarize the plasma membrane in a PKA independent cascade.

cell biology↗

bioRxiv2020

Patient-specific optimization of automated detection improves seizure onset zone localization based on high frequency oscillations

ObjectiveHigh frequency oscillations (HFOs) are a biomarker of the seizure onset zone (SOZ) and can be visually or automatically detected. In theory, one can optimize an automated algorithms parameters to maximize SOZ localization accuracy; however, there is no consensus on whether or how this should be done. Therefore, we optimized an automated detector using visually identified HFOs and evaluated the impact on SOZ localization accuracy. MethodsWe detected HFOs in intracranial EEG from 20 patients with refractory epilepsy from two centers using (1) unoptimized automated detection, (2) visual identification, and (3) automated detection optimized to match visually detected HFOs. ResultsSOZ localization accuracy based on HFO rate was not significantly different between the three methods. Across patients, visually optimized detector settings varied, and no single set of settings produced universally accurate SOZ localization. Exploratory analysis suggests that, for many patients, detection settings exist that would improve SOZ localization. ConclusionsSOZ localization accuracy was similar for all three methods, was not improved by visually optimizing detector settings, and may benefit from patient-specific parameter optimization. SignificanceVisual HFO marking is laborious, and optimizing automated detection using visual markings does not improve localization accuracy. New patient-specific detector optimization methods are needed.

neuroscience↗

bioRxiv2019

Capacitation-associated alkalization in human sperm is differentially controlled at the subcellular level

Capacitation in mammalian sperm involves the accurate balance of intracellular pH (pHi), but the underlying control mechanisms are not fully understood, particularly regarding the spatiotemporal regulation of the proteins involved in such pHi modulation. Here we employed an image-based flow cytometry technique combined with pharmacological approaches to study pHi dynamics at the subcellular level during sperm capacitation. We found that, upon capacitation induction, sperm cells undergo intracellular alkalization in the head and principal piece regions, but not in the midpiece. The observed localized pHi increases require the initial uptake of HCO3-, and it is mediated by several proteins acting in a manner consistent with their subcellular localization. Hv1 proton channel and cAMP-activated Protein Kinase (PKA) antagonists impair alkalization mainly in the principal piece. Na+/HCO3- cotransporter (NBC) and cystic fibrosis transmembrane regulator (CFTR) antagonists impair alkalization only mildly, predominantly in the head. Motility measurements indicate that inhibition of alkalization in the principal piece prevents the development of hyperactivated motility. Altogether, our findings shed light into the complex control mechanisms of pHi and underscore their importance during human sperm capacitation.\n\nSummary statementHuman sperm display differential pHi regulation at the subcellular level upon capacitation, involving the participation of PKA kinase signaling pathway and several membrane transport proteins, culminating in hyperactivation.

cell biology↗