A genetically encoded secreted toxin potentiates synaptic NMDA receptors in hippocampal neurons and confers neuroprotection.

NMDA receptors (NMDARs) play essential roles in neuronal development, survival, and synaptic plasticity, to name a few. However, dysregulation in receptors' activity can lead to neuronal and synaptic damage, contributing to the development of various brain pathologies. Current pharmacological treatments targeting NMDARs remain limited, for instance due to insufficient receptor selectivity and poor spatial targeting.

Tripartite interactions of PKA catalytic subunit and C-terminal domains of cardiac Ca channel may modulate its β-adrenergic regulation.

Background: The β-adrenergic augmentation of cardiac contraction, by increasing the conductivity of L-type voltage-gated Ca1.2 channels, is of great physiological and pathophysiological importance. Stimulation of β-adrenergic receptors (βAR) activates protein kinase A (PKA) through separation of regulatory (PKAR) from catalytic (PKAC) subunits.

Revealing the MRI-Contrast in Optically Cleared Brains.

The current consensus holds that optically-cleared specimens are unsuitable for Magnetic Resonance Imaging (MRI); exhibiting absence of contrast. Prior studies combined MRI with tissue-clearing techniques relying on the latter's ability to eliminate lipids, thereby fostering the assumption that lipids constitute the primary source of ex vivo MRI-contrast. Nevertheless, these findings contradict an extensive body of literature that underscores the contribution of other features to contrast.

Datasets assessing lipid-content in optically cleared brains.

Multi-modal imaging, by light-microscopy (LM) and Magnetic Resonance Imaging (MRI), holds promise for examining the brain across various resolutions and scales. While MRI acquires images in three dimensions, acquisition of intact whole-brain by LM requires a process of tissue clearing that renders the brain transparent. Removal of lipids (delipidation) is a critical step in the tissue clearing process, and was previsouly suggested to be the cause for absence of MRI contrast in cleared brains.

SNAP-Tag-Targeted MRI-Fluorescent Multimodal Probes.

Magnetic resonance imaging (MRI) is a powerful imaging modality, widely employed in research and clinical settings. However, MRI images suffer from low signals and a lack of target specificity. We aimed to develop a multimodal imaging probe to detect targeted cells by MRI and fluorescence microscopy.

Reduction in Filamin C transcript is associated with arrhythmogenic cardiomyopathy in Ashkenazi Jews.

Background: Filamin C is a cytoskeletal protein expressed in cardiac cells. Nonsense variations in the filamin C gene (FLNC) were associated with dilated and arrhythmogenic cardiomyopathies.

Methods And Results: We identified an intronic variation in FLNC gene (c.

Andersen-Tawil Syndrome Is Associated With Impaired PIP Regulation of the Potassium Channel Kir2.1.

Andersen-Tawil syndrome (ATS) type-1 is associated with loss-of-function mutations in gene. encodes the tetrameric inward-rectifier potassium channel Kir2.1, important to the resting phase of the cardiac action potential.

Protein kinase A regulates C-terminally truncated Ca 1.2 in Xenopus oocytes: roles of N- and C-termini of the α subunit.

Key Points: β-Adrenergic stimulation enhances Ca entry via L-type Ca 1.2 channels, causing stronger contraction of cardiac muscle cells. The signalling pathway involves activation of protein kinase A (PKA), but the molecular details of PKA regulation of Ca 1.

Regulation of cardiac L-type Ca²⁺ channel CaV1.2 via the β-adrenergic-cAMP-protein kinase A pathway: old dogmas, advances, and new uncertainties.

In the heart, adrenergic stimulation activates the β-adrenergic receptors coupled to the heterotrimeric stimulatory Gs protein, followed by subsequent activation of adenylyl cyclase, elevation of cyclic AMP levels, and protein kinase A (PKA) activation. One of the main targets for PKA modulation is the cardiac L-type Ca²⁺ channel (CaV1.2) located in the plasma membrane and along the T-tubules, which mediates Ca²⁺ entry into cardiomyocytes.

SK4 Ca2+ activated K+ channel is a critical player in cardiac pacemaker derived from human embryonic stem cells.

Proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. Two main mechanisms have been proposed: (i) the "voltage-clock," where the hyperpolarization-activated funny current If causes diastolic depolarization that triggers action potential cycling; and (ii) the "Ca(2+) clock," where cyclical release of Ca(2+) from Ca(2+) stores depolarizes the membrane during diastole via activation of the Na(+)-Ca(2+) exchanger. Nonetheless, these mechanisms remain controversial.

Competitive and non-competitive regulation of calcium-dependent inactivation in CaV1.2 L-type Ca2+ channels by calmodulin and Ca2+-binding protein 1.

CaV1.2 interacts with the Ca(2+) sensor proteins, calmodulin (CaM) and calcium-binding protein 1 (CaBP1), via multiple, partially overlapping sites in the main subunit of CaV1.2, α1C.

Early infantile epileptic encephalopathy associated with a high voltage gated calcium channelopathy.

Background: Early infantile epileptic encephalopathies usually manifest as severely impaired cognitive and motor development and often result in a devastating permanent global developmental delay and intellectual disability. A large set of genes has been implicated in the aetiology of this heterogeneous group of disorders. Among these, the ion channelopathies play a prominent role.

Modulation of distinct isoforms of L-type calcium channels by G(q)-coupled receptors in Xenopus oocytes: antagonistic effects of Gβγ and protein kinase C.

L-type voltage dependent Ca(2+) channels (L-VDCCs; Ca(v)1.2) are crucial in cardiovascular physiology. In heart and smooth muscle, hormones and transmitters operating via G(q) enhance L-VDCC currents via essential protein kinase C (PKC) involvement.

CaBP1 regulates voltage-dependent inactivation and activation of Ca(V)1.2 (L-type) calcium channels.

CaBP1 is a Ca(2+)-binding protein that regulates the gating of voltage-gated (Ca(V)) Ca(2+) channels. In the Ca(V)1.2 channel α(1)-subunit (α(1C)), CaBP1 interacts with cytosolic N- and C-terminal domains and blunts Ca(2+)-dependent inactivation.

Characterization of the calmodulin-binding site in the N terminus of CaV1.2.

Interaction of calmodulin (CaM) with the C-terminus (CT) of the L-type Ca(V)1.2 channel is crucial for Ca(2+)-dependent inactivation (CDI). CaM also binds to the N-terminus (NT), and a CaM-formed "bridge" between CT and NT has been proposed to control CDI.