Large conductance voltage-and calcium-activated K (BK) channel in health and disease.

Large Conductance Voltage- and Calcium-activated K (BK) channels are transmembrane pore-forming proteins that regulate cell excitability and are also expressed in non-excitable cells. They play a role in regulating vascular tone, neuronal excitability, neurotransmitter release, and muscle contraction. Dysfunction of the BK channel can lead to arterial hypertension, hearing disorders, epilepsy, and ataxia.

A journey from molecule to physiology and tools for drug discovery targeting the transient receptor potential vanilloid type 1 (TRPV1) channel.

The heat and capsaicin receptor TRPV1 channel is widely expressed in nerve terminals of dorsal root ganglia (DRGs) and trigeminal ganglia innervating the body and face, respectively, as well as in other tissues and organs including central nervous system. The TRPV1 channel is a versatile receptor that detects harmful heat, pain, and various internal and external ligands. Hence, it operates as a polymodal sensory channel.

Congenital Cytomegalovirus Awareness and Knowledge among Health Professionals and Pregnant Women: An Action towards Prevention.

Introduction: Cytomegalovirus (CMV) is a major cause of childhood disabilities, and consensus recommendations emphasize the importance of hygienic measures to reduce perinatal infection. Our study aimed to evaluate the level of awareness about CMV among health professionals and pregnant women.

Methods: We submitted a 20-item online survey regarding CMV perinatal infection to all obstetricians and midwives in Catalonia (Spain) and a 7-item lay version of the questionnaire to 700 pregnant women.

Fetal Liver Volume Assessment Using Magnetic Resonance Imaging in Fetuses With Cytomegalovirus Infection.

Objective: To assess fetal liver volume (FLV) by magnetic resonance imaging (MRI) in cytomegalovirus (CMV)-infected fetuses compared to a group of healthy fetuses.

Method: Most infected cases were diagnosed by the evidence of ultrasound abnormalities during routine scans and in some after maternal CMV screening. CMV-infected fetuses were considered severely or mildly affected according to prenatal brain lesions identified by ultrasound (US)/MRI.

Young Argentine Children's Attributions about Hypothetical Socially Withdrawn Peers.

This study assessed young children's attributions about different subtypes of hypothetical socially withdrawn peers. Participants were  = 114 (56% boys, = 60.53 months,  = 7.

Bisphosphonates Targeting Ion Channels and Musculoskeletal Effects.

Bisphosphonates (BPs) are the most used bone-specific anti-resorptive agents, often chosen as first-line therapy in several bone diseases characterized by an imbalance between osteoblast-mediated bone production and osteoclast-mediated bone resorption. BPs target the farnesyl pyrophosphate synthase (FPPS) in osteoclasts, reducing bone resorption. Lately, there has been an increasing interest in BPs direct pro-survival/pro-mineralizing properties in osteoblasts and their pain-relieving effects.

Correction: Prion Protein Misfolding Affects Calcium Homeostasis and Sensitizes Cells to Endoplasmic Reticulum Stress.

[This corrects the article DOI: 10.1371/journal.pone.

Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1.

Programmed cell death is regulated by the balance between activating and inhibitory signals. Here, we have identified RECS1 (responsive to centrifugal force and shear stress 1) [also known as TMBIM1 (transmembrane BAX inhibitor motif containing 1)] as a proapoptotic member of the TMBIM family. In contrast to other proteins of the TMBIM family, RECS1 expression induces cell death through the canonical mitochondrial apoptosis pathway.

Physiological and affective responses to emoji faces: Effects on facial muscle activity, skin conductance, heart rate, and self-reported affect.

The objective of the present study was to evaluate emotional responses to emoji faces through physiological and self-report measures, and evaluate possible differences between men and women. One hundred participants (50 women) observed pictures of happy, neutral, and angry emoji faces, while activity of the zygomatic and corrugator muscles, skin conductance, and heart rate were measured. Self-report measures of emotional experience were also recorded.

Effects of Interleukin-1β in Glycinergic Transmission at the Central Amygdala.

Interleukin-1β (IL-1β) is an important cytokine that modulates peripheral and central pain sensitization at the spinal level. Among its effects, it increases spinal cord excitability by reducing inhibitory Glycinergic and GABAergic neurotransmission. In the brain, IL-1β is released by glial cells in regions associated with pain processing during neuropathic pain.

Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit.

Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca- and voltage-dependent K channel (BK) in vascular smooth muscle depending on the expression of the auxiliary β1 subunit. Here, using the patch-clamp technique on BK channel co-expressed with β1 subunit in a heterologous cell expression system, we analyzed whether AA modifies the three functional modules involved in the channel gating: the voltage sensor domain (VSD), the pore domain (PD), and the intracellular calcium sensor domain (CSD).

A folding reaction at the C-terminal domain drives temperature sensing in TRPM8 channels.

In mammals, temperature-sensitive TRP channels make membrane conductance of cells extremely temperature dependent, allowing the detection of temperature ranging from noxious cold to noxious heat. We progressively deleted the distal carboxyl terminus domain (CTD) of the cold-activated melastatin receptor channel, TRPM8. We found that the enthalpy change associated with channel gating is proportional to the length of the CTD.

TRPV1-Estradiol Stereospecific Relationship Underlies Cell Survival in Oxidative Cell Death.

17β-estradiol is a neuronal survival factor against oxidative stress that triggers its protective effect even in the absence of classical estrogen receptors. The polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channel has been proposed as a steroid receptor implied in tissue protection against oxidative damage. We show here that TRPV1 is sufficient condition for 17β-estradiol to enhance metabolic performance in injured cells.

Calcium-driven regulation of voltage-sensing domains in BK channels.

Allosteric interactions between the voltage-sensing domain (VSD), the Ca-binding sites, and the pore domain govern the mammalian Ca- and voltage-activated K (BK) channel opening. However, the functional relevance of the crosstalk between the Ca- and voltage-sensing mechanisms on BK channel gating is still debated. We examined the energetic interaction between Ca binding and VSD activation by investigating the effects of internal Ca on BK channel gating currents.

The molecular nature of the 17β-Estradiol binding site in the voltage- and Ca-activated K (BK) channel β1 subunit.

The accessory β1 subunit modulates the Ca- and voltage-activated K (BK) channel gating properties mainly by increasing its apparent Ca sensitivity. β1 plays an important role in the modulation of arterial tone and blood pressure by vascular smooth muscle cells (SMCs). 17β-estradiol (E2) increases the BK channel open probability (P) in SMCs, through a β1 subunit-dependent modulatory effect.

[Effectiveness of cigarette-pack warning labels in capturing the attention of smokers and nonsmokersEficácia das tarjas de advertência em maços de cigarro para atrair a atenção de fumantes e não fumantes].

Objective: To determine the ability of cigarette-pack warning labels, of the minimum size required by the World Health Organization, to capture the attention of smokers and nonsmokers.

Methods: In this study, 30 smokers and 30 nonsmokers completed a dot-probe task in which they simultaneously observed images of cigarette packs split in two: the top contained the cigarette brand and the bottom contained the warning label. During the task, brain activity was recorded through two event-related potentials of the negative-polarity type--the potential that occurs in the posterior-contralateral zone approximately 200 ms after a stimulus (N2pc) and the sustained posterior contralateral negativity (SPCN) response--which are indicators of early and sustained attention.

Methods for Investigating TRP Channel Gating.

A complete characterization of temperature -and voltage-activated TRP channel gating requires a precise determination of the absolute probability of opening in a wide range of voltages, temperatures, and agonist concentrations. We have achieved this in the case of the TRPM8 channel expressed in Xenopus laevis oocytes. Measurements covered an extensive range of probabilities and unprecedented applied voltages up to 500 mV.

Thermally activated TRP channels: molecular sensors for temperature detection.

Temperature sensing is one of the oldest capabilities of living organisms, and is essential for sustaining life, because failure to avoid extreme noxious temperatures can result in tissue damage or death. A subset of members of the transient receptor potential (TRP) ion channel family is finely tuned to detect temperatures ranging from extreme cold to noxious heat, giving rise to thermoTRP channels. Structural and functional experiments have shown that thermoTRP channels are allosteric proteins, containing different domains that sense changes in temperature, among other stimuli, triggering pore opening.

BAX inhibitor-1 regulates autophagy by controlling the IRE1α branch of the unfolded protein response.

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Molecular Determinants of BK Channel Functional Diversity and Functioning.

Large-conductance Ca- and voltage-activated K (BK) channels play many physiological roles ranging from the maintenance of smooth muscle tone to hearing and neurosecretion. BK channels are tetramers in which the pore-forming α subunit is coded by a single gene (Slowpoke, KCNMA1). In this review, we first highlight the physiological importance of this ubiquitous channel, emphasizing the role that BK channels play in different channelopathies.

Voltage-dependent BK and Hv1 channels expressed in non-excitable tissues: New therapeutics opportunities as targets in human diseases.

Voltage-gated ion channels are the molecular determinants of cellular excitability. This group of ion channels is one of the most important pharmacological targets in excitable tissues such as nervous system, cardiac and skeletal muscle. Moreover, voltage-gated ion channels are expressed in non-excitable cells, where they mediate key cellular functions through intracellular biochemical mechanisms rather than rapid electrical signaling.