Primary cortical neurons form calcium-phosphate sheets with a bone-precursor-like ultrastructure.

Calcium-phosphate is a critical component in healthy bone and teeth formation, but its pathologic buildup in brain can occur in dyshomeostatic calcium disorders like Alzheimer's disease and Leigh syndrome. Extracellular calcium-phosphate in the nervous system is not well understood, but prior evidence suggests mitochondria as a potential source. Recently, large unidentified double-membrane-bound hyper-electron dense sheet aggregates of unknown content were reported in Huntington's disease model neurons using cryo-ET that were absent in wild-type control neurons.

FGF12A Regulates Nav1.5 via CaM-regulated and CaM-independent Mechanisms.

Opening of the cardiac voltage-gated Na+ channel (Nav1.5) is responsible for robust depolarization of the cardiac action potential, while inactivation, which rapidly follows, allows for repolarization. Regulation of both the voltage- and time-dependent kinetics of Nav1.

Targeting Tiam1 Enhances Hippocampal-Dependent Learning and Memory in the Adult Brain and Promotes NMDA Receptor-Mediated Synaptic Plasticity and Function.

Excitatory synapses and the actin-rich dendritic spines on which they reside are indispensable for information processing and storage in the brain. In the adult hippocampus, excitatory synapses must balance plasticity and stability to support learning and memory. However, the mechanisms governing this balance remain poorly understood.

Arrhythmia-associated calmodulin variants interact with KCNQ1 to confer aberrant membrane trafficking and function.

Missense variants in calmodulin (CaM) predispose patients to arrhythmias associated with high mortality rates ("calmodulinopathy"). As CaM regulates many key cardiac ion channels, an understanding of disease mechanism associated with CaM variant arrhythmias requires elucidating individual CaM variant effects on distinct channels. One key CaM regulatory target is the KCNQ1 (K7.

Differential regulation of cardiac sodium channels by intracellular fibroblast growth factors.

Voltage-gated sodium (NaV) channels are responsible for the initiation and propagation of action potentials. In the heart, the predominant NaV1.5 α subunit is composed of four homologous repeats (I-IV) and forms a macromolecular complex with multiple accessory proteins, including intracellular fibroblast growth factors (iFGF).

Arrhythmia-associated Calmodulin Variants Interact with KCNQ1 to Confer Aberrant Membrane Trafficking and Function.

Rationale: Missense variants in calmodulin (CaM) predispose patients to arrhythmias associated with high mortality rates. As CaM regulates several key cardiac ion channels, a mechanistic understanding of CaM variant-associated arrhythmias requires elucidating individual CaM variant effect on distinct channels. One key CaM regulatory target is the KCNQ1 (K 7.

An allosteric modulator activates BK channels by perturbing coupling between Ca binding and pore opening.

BK type Ca-activated K channels activate in response to both voltage and Ca. The membrane-spanning voltage sensor domain (VSD) activation and Ca binding to the cytosolic tail domain (CTD) open the pore across the membrane, but the mechanisms that couple VSD activation and Ca binding to pore opening  are not clear. Here we show that a compound, BC5, identified from in silico screening, interacts with the CTD-VSD interface and specifically modulates the Ca dependent activation mechanism.