Ahf-Caltide, a Novel Polypeptide Derived from Calpastatin, Protects against Oxidative Stress Injury by Stabilizing the Expression of Ca1.2 Calcium Channel.

Reperfusion after ischemia would cause massive myocardial injury, which leads to oxidative stress (OS). Calcium homeostasis imbalance plays an essential role in myocardial OS injury. Ca1.

Regulation of Cardiac Cav1.2 Channels by Calmodulin.

Cav1.2 Ca channels, a type of voltage-gated L-type Ca channel, are ubiquitously expressed, and the predominant Ca channel type, in working cardiac myocytes. Cav1.

Ca Dyshomeostasis Links Risk Factors to Neurodegeneration in Parkinson's Disease.

Parkinson's disease (PD), a common neurodegenerative disease characterized by motor dysfunction, results from the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Although the precise causes of PD are still unknown, several risk factors for PD have been determined, including aging, genetic mutations, environmental factors, and gender. Currently, the molecular mechanisms underlying risk factor-related neurodegeneration in PD remain elusive.

Properties of Calmodulin Binding to Na1.2 IQ Motif and Its Autism-Associated Mutation R1902C.

Voltage-gated sodium channels (VGSCs) are fundamental to the initiation and propagation of action potentials in excitable cells. Ca/calmodulin (CaM) binds to VGSC type II (Na1.2) isoleucine and glutamine (IQ) motif.

TASK channels: channelopathies, trafficking, and receptor-mediated inhibition.

TWIK-related acid-sensitive K (TASK) channels contribute to the resting membrane potential in various kinds of cells, such as brain neurons, smooth muscle cells, and endocrine cells. Loss-of-function mutations at multiple sites in the KCNK3 gene encoding for TASK1 channels are one of the causes of pulmonary arterial hypertension in humans, whereas a mutation at only one site is reported for TASK3 channels, resulting in a syndrome of mental retardation, hypotonia, and facial dysmorphism. TASK channels are subject to regulation by G protein-coupled receptors (GPCRs).

The LQT-associated calmodulin mutant E141G induces disturbed Ca-dependent binding and a flickering gating mode of the Ca1.2 channel.

Calmodulin (CaM) mutations are associated with congenital long QT (LQT) syndrome (LQTS), which may be related to the dysregulation of the cardiac-predominant Ca channel isoform Ca1.2. Among various mutants, CaM-E141G was identified as a critical missense variant.

Purification of insoluble GST-fused and GST-cleaved Cav1.2 channel fragment by denaturation and renaturation.

Both recombinant glutathione-S-transferase (GST)-fused and GST-cleaved fragments of an L-type voltage-gated Ca channel (Cav1.2) are used frequently in GST pull-down assays to investigate the interactions between regulatory proteins and the Cav1.2 channel.

The Effect of Ca, Lobe-Specificity, and CaMKII on CaM Binding to Na1.1.

Calmodulin (CaM) is well known as an activator of calcium/calmodulin-dependent protein kinase II (CaMKII). Voltage-gated sodium channels (VGSCs) are basic signaling molecules in excitable cells and are crucial molecular targets for nervous system agents. However, the way in which Ca/CaM/CaMKII cascade modulates Na1.

PKA phosphorylation of Cav1.2 channel modulates the interaction of calmodulin with the C terminal tail of the channel.

Activity of cardiac Cav1.2 channels is enhanced by cyclic AMP-PKA signaling. In this study, we studied the effects of PKA phosphorylation on the binding of calmodulin to the fragment peptide of the proximal C-terminal tail of α1C subunit (CT1, a.

A novel role of the antitumor agent tricyclodecan-9-yl-xanthogenate as an open channel blocker of KCNQ1/KCNE1.

Tricyclodecan-9-yl-xanthogenate (D609) is widely known for its antitumor and antiviral properties via the inhibition of phosphatidylcholine-specific phospholipase C and sphingomyelin synthase. Previously, we found that chronic application of D609 suppressed the K channel, KCNQ1/KCNE1, more drastically than expected from its actions on the enzymes, suggesting a direct action of D609 on the channel. Here, we aimed to test this possibility by studying the affinity, specificity, and mechanisms of D609 on KCNQ1/KCNE1.

A new interaction between proximal and distal C-terminus of Cav1.2 channels.

Cardiac Cav1.2 channels, coupling membrane stimulation to intracellular Ca signaling, are regulated by multiple cytoplasmic factors, such as calmodulin (CaM), phosphorylation, Ca, ATP and intramolecular fragments of the channel. The interaction between distal and proximal C-terminal regulatory domains (DCRD and PCRD) of Cav1.

Calmodulin and ATP support activity of the Cav1.2 channel through dynamic interactions with the channel.

Key Points: Cav1.2 channels maintain activity through interactions with calmodulin (CaM). In this study, activities of the Cav1.

Role of protein phosphatases in the run down of guinea pig cardiac Cav1.2 Ca2+ channels.

This study aimed to investigate protein phosphatases involved in the run down of Cav1.2 Ca(2+) channels. Single ventricular myocytes obtained from adult guinea pig hearts were used to record Ca(2+) channel currents with the patch-clamp technique.

PKA and phosphatases attached to the Ca(V)1.2 channel regulate channel activity in cell-free patches.

Calmodulin (CaM) + ATP can reprime voltage-gated L-type Ca(2+) channels (Ca(V)1.2) in inside-out patches for activation, but this effect decreases time dependently. This suggests that the Ca(V)1.

Mg(2+)-dependent facilitation and inactivation of L-type Ca(2+) channels in guinea pig ventricular myocytes.

This study aimed to investigate the intracellular Mg(2+) regulation of the L-type Ca(2+) channels in guinea pig ventricular myocytes. By adopting the inside-out configuration of the patch clamp technique, single channel currents of the L-type Ca(2+) channels were recorded at different intracellular Mg(2+) concentrations ([Mg(2+)]i). At free [Mg(2+)]i of 0, 10(-9), 10(-7), 10(-5), 10(-3), and 10(-1) M, 1.

Regulation of the Cav1.2 cardiac channel by redox via modulation of CaM interaction with the channel.

Although it has been well documented that redox can modulate Cav1.2 channel activity, the underlying mechanisms are not fully understood. In our study, we examined the effects of redox on Cav1.

Nucleotides maintain the activity of Cav1.2 channels in guinea-pig ventricular myocytes.

The activity of Cav1.2 Ca(2+) channels is maintained in the presence of calmodulin and ATP, even in cell-free patches, and thus a channel ATP-binding site has been suggested. In this study, we examined whether other nucleotides, such as GTP, UTP, CTP, ADP and AMP, could be substituted for ATP in guinea-pig ventricular myocytes.

The individual N- and C-lobes of calmodulin tether to the Cav1.2 channel and rescue the channel activity from run-down in ventricular myocytes of guinea-pig heart.

The present study examined the binding of the individual N- and C-lobes of calmodulin (CaM) to Cav1.2 at different Ca(2+) concentration ([Ca(2+)]) from ≈ free to 2mM, and found that they may bind to Cav1.2 Ca(2+)-dependently.

A new phosphorylation site in cardiac L-type Ca2+ channels (Cav1.2) responsible for its cAMP-mediated modulation.

Cardiac L-type Ca(2+) channels are modulated by phosphorylation by protein kinase A (PKA). To explore the PKA-targeted phosphorylation site(s), five potential phosphorylation sites in the carboxyl (COOH) terminal region of the α1C-subunit of the guinea pig Cav1.2 Ca(2+) channel were mutated by replacing serine (S) or threonine (T) residues with alanine (A): S1574A (C1 site), S1626A (C2), S1699A (C3), T1908A, (C4), S1927A (C5), and their various combinations.

Adenosine triphosphate regulates the activity of guinea pig Cav1.2 channel by direct binding to the channel in a dose-dependent manner.

The present study is to investigate the mechanism by which ATP regulates Cav1.2 channel activity. Ventricular tissue was obtained from adult guinea pig hearts using collagenase.

The Ca(2+)-dependent interaction of calpastatin domain L with the C-terminal tail of the Cav1.2 channel.

To demonstrate the interaction of calpastatin (CS) domain L (CSL) with Cav1.2 channel, we investigated the binding of CSL with various C-terminus-derived peptides at≈free, 100 nM, 10 μM, and 1mM Ca(2+) by using the GST pull-down assay method. Besides binding with the IQ motif, CSL was also found to bind with the PreIQ motif.

Mechanisms underlying the modulation of L-type Ca2+ channel by hydrogen peroxide in guinea pig ventricular myocytes.

Although Cav1.2 Ca(2+) channels are modulated by reactive oxygen species (ROS), the underlying mechanisms are not fully understood. In this study, we investigated effects of hydrogen peroxide (H2O2) on the Ca(2+) channel using a patch-clamp technique in guinea pig ventricular myocytes.

Lobe-related concentration- and Ca(2+)-dependent interactions of calmodulin with C- and N-terminal tails of the CaV1.2 channel.

This study examined the bindings of calmodulin (CaM) and its mutants with the C- and N-terminal tails of the voltage-gated Ca(2+) channel CaV1.2 at different CaM and Ca(2+) concentrations ([Ca(2+)]) by using the pull-down assay method to obtain basic information on the binding mode, including its concentration- and Ca(2+)-dependencies. Our data show that more than one CaM molecule could bind to the CaV1.

Differential relationships between personality and brain function in monetary and goal-oriented subjective motivation: multichannel near-infrared spectroscopy of healthy subjects.

Aim: To examine relationships between personality traits and cerebral cortex reactivity under different motivating conditions.

Methods: Relationships between personality traits assessed using the NEO Personality Inventory-Revised (NEO-PI-R) and cerebral cortex reactivity during a verbal fluency task monitored using multichannel near-infrared spectroscopy (NIRS) were examined under three different motivational conditions: control, monetary reward, and goal-oriented, in healthy young male volunteers.

Results: Significant correlations between cerebral cortex reactivity and personality traits were found in the frontopolar region: a positive correlation with agreeableness and a negative correlation with the neuroticism and conscientiousness scores of the NEO-PI-R under the three motivational conditions.