Neurotransmission is critical for brain function, allowing neurons to communicate through neurotransmitters and neuropeptides. RVD-hemopressin (RVD-Hp), a novel peptide identified in noradrenergic neurons, modulates cannabinoid receptors CB1 and CB2. Unlike hemopressin (Hp), which induces anxiogenic behaviors via transient receptor potential vanilloid 1 (TRPV1) activation, RVD-Hp counteracts these effects, suggesting that it may block TRPV1.
View Article and Find Full Text PDFTRPM7 (transient receptor potential cation channel subfamily M member 7) is a chanzyme with channel and kinase domains essential for embryo development. Using gamete-specific Trpm7-null lines, we report that TRPM7-mediated Mg influx is indispensable for reaching the blastocyst stage. TRPM7 is expressed dynamically from gametes to blastocysts; displays stage-specific localization on the plasma membrane, cytoplasm, and nucleus; and undergoes cleavage that produces C-terminal kinase fragments.
View Article and Find Full Text PDFHypoxia is a condition characterized by a reduction of cellular oxygen levels derived from alterations in oxygen balance. Hypoxic events trigger changes in cell-signaling cascades, oxidative stress, activation of pro-inflammatory molecules, and growth factors, influencing the activity of various ion channel families and leading to diverse cardiovascular diseases such as myocardial infarction, ischemic stroke, and hypertension. The large-conductance, calcium and voltage-activated potassium channel (BK) has a central role in the mechanism of oxygen (O) sensing and its activity has been related to the hypoxic response.
View Article and Find Full Text PDFFertilization by multiple sperm leads to lethal chromosomal number abnormalities, failed embryo development, and miscarriage. In some vertebrate and invertebrate eggs, the so-called cortical reaction contributes to their activation and prevents polyspermy during fertilization. This process involves biogenesis, redistribution, and subsequent accumulation of cortical granules (CGs) at the female gamete cortex during oogenesis.
View Article and Find Full Text PDFCa2+ influx during oocyte maturation and after sperm entry is necessary to fill the internal Ca2+ stores and for complete egg activation. We knocked out the transient receptor potential vanilloid member 3 (TRPV3) and the T-type channel, CaV3.2, to determine their necessity for maintaining these functions in mammalian oocytes/eggs.
View Article and Find Full Text PDFClin Transl Immunology
March 2021
The new coronavirus SARS-CoV-2 is a global pandemic and a severe public health crisis. SARS-CoV-2 is highly contagious and shows high mortality rates, especially in elderly and patients with pre-existing medical conditions. At the current stage, no effective drugs are available to treat these patients.
View Article and Find Full Text PDFVarious families of ion channels have been characterized in mesenchymal stem cells (MSCs), including some members of transient receptor potential (TRP) channels family. TRP channels are involved in critical cellular processes as differentiation and cell proliferation. Here, we analyzed the expression of TRPM8 channel in human bone marrow MSCs (hBM-MSCs), and its relation with osteogenic differentiation.
View Article and Find Full Text PDFPrior to maturation, mouse oocytes are arrested at the germinal vesicle (GV) stage during which they experience constitutive calcium (Ca) influx and spontaneous Ca oscillations. The oscillations cease during maturation but Ca influx continues, as the oocytes' internal stores attain maximal content at the culmination of maturation, the metaphase II stage. The identity of the channel(s) that underlie this Ca influx has not been completely determined.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2018
The success of mammalian development following fertilization depends on a series of transient increases in egg cytoplasmic Ca, referred to as Ca oscillations. Maintenance of these oscillations requires Ca influx across the plasma membrane, which is mediated in part by T-type, Ca3.2 channels.
View Article and Find Full Text PDFThe proper maturation of both male and female gametes is essential for supporting fertilization and the early embryonic divisions. In the ovary, immature fully-grown oocytes that are arrested in prophase I of meiosis I are not able to support fertilization. Acquiring fertilization competence requires resumption of meiosis which encompasses the remodeling of multiple signaling pathways and the reorganization of cellular organelles.
View Article and Find Full Text PDFVoltage-gated calcium (Ca) channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. Ca channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, Ca1.
View Article and Find Full Text PDFModulation of endothelial calcium-activated potassium (K) channels has been proposed as an approach to restore endothelial function. The present study investigated whether novel openers of K channels with small (K2.x) and intermediate (K3.
View Article and Find Full Text PDFThe Transient Receptor Potential (TRP) channels are a family of cationic ion channels widely distributed in mammalian tissues. In general, the global genetic disruption of individual TRP channels result in phenotypes associated with impairment of a particular tissue and/or organ function. An exception is the genetic ablation of the TRP channel TRPM7, which results in early embryonic lethality.
View Article and Find Full Text PDFFertilization in mammals is initiated when a sperm fuses with a mature MII oocyte, also known as egg, and triggers a plethora of finely controlled processes identified as egg activation. The completion of all events of egg activation is driven by and depends on a series of repetitive calcium (Ca(2+)) increases (Ca(2+) oscillations), which rely on Ca(2+) influx from the extracellular media. Ca(2+) channels on the egg plasma membrane (PM) are thought to mediate this influx.
View Article and Find Full Text PDFIn mammals, calcium influx is required for oocyte maturation and egg activation. The molecular identities of the calcium-permeant channels that underlie the initiation of embryonic development are not established. Here, we describe a transient receptor potential (TRP) ion channel current activated by TRP agonists that is absent in TrpV3(-/-) eggs.
View Article and Find Full Text PDFHv1 voltage-gated proton channels mediate rapid and selective transmembrane H(+) flux and are gated by both voltage and pH gradients. Selective H(+) transfer in membrane proteins is commonly achieved by Grotthuss proton 'hopping' in chains of ionizable amino acid side chains and intraprotein water molecules. To identify whether ionizable residues are required for proton permeation in Hv1, we neutralized candidate residues and measured expressed voltage-gated H(+) currents.
View Article and Find Full Text PDFObjective: To assess determinants of access to primary care services prior to pregnancy by pregnant adolescents.
Methods: Theory-based cross-sectional study conducted to examine access to heath services at five dimensions: geographic, economic, administrative, psychosocial and information. There were included in the study 200 first-time pregnant adolescents (aged 10 to 19 years) who attended a primary care unit in the municipality of Indaiatuba, Southeastern Brazil, in 2003.
Objectives: To study knowledge of some aspects of the female reproductive anatomy and physiology and their association with socio-demographic and reproductive "choices" of pregnant adolescents.
Methods: A cross-sectional study was performed with 200 first time pregnant adolescents who attended a public women's health clinic in the municipality of Indaiatuba, Sao Paulo, Brazil. During their first prenatal care visit, face-to-face interviews were conducted using a structured questionnaire and a three-dimensional handmade female model.
The internal vestibule of large-conductance Ca(2+) voltage-activated K(+) (BK) channels contains a ring of eight negative charges not present in K(+) channels of lower conductance (Glu386 and Glu389 in hSlo) that modulates channel conductance through an electrostatic mechanism (Brelidze, T.I., X.
View Article and Find Full Text PDFThe movement of ions across cell membranes is essential for a wide variety of fundamental physiological processes, including secretion, muscle contraction, and neuronal excitation. This movement is possible because of the presence in the cell membrane of a class of integral membrane proteins dubbed ion channels. Ion channels, thanks to the presence of aqueous pores in their structure, catalyze the passage of ions across the otherwise ion-impermeable lipid bilayer.
View Article and Find Full Text PDFHigh conductance, calcium- and voltage-activated potassium (BK, MaxiK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (beta) subunits. The most remarkable effects of beta1 and beta2 subunits are an increase of the calcium sensitivity and the slow down of channel kinetics.
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