Chien-Chang Chen

Academia Sinica · Institute of Biomedical Sciences

The Cav3.2 T-channel plays a pivotal role in inducing calcineurin/nuclear factor of activated T cell (NFAT) signaling during cardiac hypertrophy. Because calcineurin/NFAT signaling is induced early after pressure overload, we hypothesized that Cav3.2 is induced by an early signal. Our aim is to investigate when and how Cav3.2 is induced during card...

Cav3.2 T-type Ca2+ channel is required for the activation of calcineurin/NFAT signaling in cardiac hypertrophy. We aimed to investigate how Cav3.2 and calcineurin interact. We found that Ca2+ and calmodulin modulate the Cav3.2/calcineurin interaction. Calcineurin binding to Cav3.2 decreases the enzyme's phosphatase activity and diminishes the chann...

Treatments for chronic musculoskeletal pain, such as lower back pain, fibromyalgia, and myofascial pain syndrome, remain inadequate because of our poor understanding of the mechanisms that underlie these conditions. Although T-type Ca2+ channels (T-channels) have been implicated in peripheral and central pain sensory pathways, their role in chronic...

Voltage-gated T-type Ca(2+) channels (T-channels) are normally expressed during embryonic development in ventricular myocytes but are undetectable in adult ventricular myocytes. Interestingly, T-channels are reexpressed in hypertrophied or failing hearts. It is unclear whether T-channels play a role in the pathogenesis of cardiomyopathy and what th...

Alzheimer's disease (AD) is one of the most common progressive neurodegenerative disorders that cause deterioration of cognitive functions. Recent studies suggested that the accumulation of inflammatory molecules and impaired protein degradation mechanisms might both play a critical role in the progression of AD. Autophagy is a major protein degrad...

Background: Cav 3.2 is a T-type calcium channel that causes low-threshold exocytosis. T-type calcium channel blockers reduce platelet granule exocytosis and aggregation. However, studies of the T-type calcium channel in platelets is lacking. Objective: To examine the expression and role of Cav 3.2 in platelet function. Methods: Global Cav 3.2-...

An amendment to this paper has been published and can be accessed via the original article.

Background: Neuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli. To date, the current pharmacological treatments for neuropathic pain are still unsatisfactory. The gut microbiota reportedly plays important roles in inducing neuropathic pain, so probiotics have also been used to treat it. H...

Background Neuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli. To date, the current pharmacological treatments for neuropathic pain are still unsatisfactory. The gut microbiota reportedly plays important roles in inducing neuropathic pain, so probiotics have also been used to treat it. How...

Background: Neuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli. To date, the current pharmacological treatments for neuropathic pain are still unsatisfactory. The gut microbiota reportedly plays important roles in inducing neuropathic pain, so probiotics have also been used to treat it. Ho...

Background: Neuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli. To date, the current pharmacological treatments for neuropathic pain are still unsatisfactory. The gut microbiota reportedly plays important roles in inducing neuropathic pain, so probiotics have also been used to treat it. Ho...

Severe infection with the re-emerging enterovirus 71 (EV71 or EV-A71) can cause cardiopulmonary failure. However, in patients’ heart and lung, viral protein has not been detected. In mouse models, heart disease has not been reported. EV71-infected brainstem is generally believed to be responsible for the cardiopulmonary collapse. One major limitati...

Abstract Pain-related diseases are the top leading causes of life disability. Identifying brain regions involved in persistent neuronal changes will provide new insights for developing efficient chronic pain treatment. Here, we showed that anterior nucleus of paraventricular thalamus (PVA) plays an essential role in the development of mechanical hy...

Memory retrieval dysfunction is a symptom of schizophrenia, autism spectrum disorder (ASD), and absence epilepsy (AE), as well as an early sign of Alzheimer's disease. To date, few drugs have been reported to enhance memory retrieval. Here, we found that a coral-derived natural product, excavatolide-B (Exc-B), enhances contextual memory retrieval i...

The original version of this Article contained an error in the affiliation of the second author, Ya-Ting Chang. The correct affiliations for Ya-Ting Chang are Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan and International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 115,...

Chronic pain can be initiated by one or more acute stimulations to sensitize neurons into the primed state. In the primed state, the basal nociceptive thresholds of the animal are normal, but in response to another hyperalgesic stimulus, the animal develops enhanced and prolonged hyperalgesia. The exact mechanism of how primed state is formed is no...

The prevalence of chronic pain increases with age. The pain occurrence in the elderly ranges from 25% to 80% in different countries. Ischemic heart disease is also prevailing in the aged people. Restored blood flow quickly rescues myocardium but also causes ischemia-reperfusion (IR) injury. Brief episodes of ischemia at a distant organ could reduce...

Background The type VI adenylyl cyclase (AC6) is a main contributor of cAMP production in the heart. The amino acid (aa) sequence of AC6 is highly homologous to that of another major cardiac adenylyl cyclase, AC5, except for its N-terminus (AC6-N, aa 1–86). Activation of AC6, rather than AC5, produces cardioprotective effects against heart failure,...

Myocardial infarction is the leading cause of death worldwide. Restoration of blood flow rescues myocardium but also causes ischemia-reperfusion injury. Here, we show that in a mouse model of chronic neuropathic pain, ischemia-reperfusion injury following myocardial infarction is reduced, and this cardioprotection is induced via an anterior nucleus...

Pathological cardiac hypertrophy, a dynamic remodeling process, is a major risk factor for heart failure. Although a number of key regulators and related genes have been identified, how the transcription factors (TFs) dynamically regulate the associated genes and control the morphological and electrophysiological changes during the hypertrophic pro...

Pluripotent-cell-derived cardiomyocytes have great potential for use in research and medicine, but limitations in their maturity currently constrain their usefulness. Here, we report a method for improving features of maturation in murine and human embryonic-stem-cell-derived cardiomyocytes (m/hESC-CMs). We found that coculturing m/hESC-CMs with e...

Homozygous Cav3.2 knockout mice, which are defective in the pore-forming subunit of a low voltage activated T-type calcium channel, have been documented to show impaired maintenance of late-phase long-term potentiation (L-LTP) and defective retrieval of context-associated fear memory. To investigate the role of Cav3.2 in global gene expression, we...

We employed a microfluidic device to study the effects of hydraulic pressure on cardiomyoblast H9c2. The 170 mm Hg pressure increased the cellular area and the expression of atrial natriuretic peptide. With the same device, we demonstrated that the effects of hydraulic pressure on the cardiomyoblast could be reduced by the inhibitor of focal adhesi...

Significance Intrinsic bursts and rhythmic burst discharges are elicited by activation of T-type Ca ²⁺ channels in the thalamic reticular nucleus (TRN). TRN bursts are believed to be critical for generation and maintenance of thalamocortical oscillations, leading to spike-and-wave discharges (SWDs) on the cortical electroencephalogram, which are th...

MicroRNAs are a class of endogenous small noncoding RNAs that regulate gene expression either by degrading target mRNAs or by suppressing protein translation. MicroRNAs have been found to be involved in many biological processes, such as development, differentiation and growth. However, the evolution of microRNA regulatory functions and networks ha...

Significance The tracheal cartilage rings are important for protecting and maintaining the airway. However, the chondrogenesis of tracheal cartilage is not completely understood. We demonstrate that the Ca v 3.2 T-type calcium channel is required for normal tracheal cartilage ring formation. Calcium influx via Ca v 3.2 induces chondrogenesis and up...

Ca ²⁺ influx is crucial in initiating the differentiation of mesenchymal cells into chondrocytes, but which Ca ²⁺ channels are involved remains uncertain. Here we show that the T‐type voltage‐gated Ca ²⁺ channel Ca v 3.2 is essential for tracheal chondrogenesis. Mice lacking this channel (Ca v 3.2 ‐/‐ ) showed congenital tracheal stenosis because o...

Pressure-overload stress to the heart causes pathological cardiac hypertrophy, which increases the risk of cardiac morbidity and mortality. However, the detailed signaling pathways induced by pressure overload remain unclear. Here we used phosphoproteomics to delineate signaling pathways in the myocardium responding to acute pressure overload and c...

AimsRestenosis is an undesirable consequence following percutaneous vascular interventions. However, the current strategy for preventing restenosis is inadequate. The aim of this study was to investigate the role of low-voltage gated T-type calcium channels in regulating vascular smooth muscle cell (VSMC) proliferation during neointimal formation.M...

Introduction: Although it is known that the Ca v 3.2 T-type calcium channel is predominantly expressed in the embryonic stage and re-expressed in adult hearts during the cardiac hypertrophy. What does regulate the reexpression of Ca v 3.2 in hearts? Hypothesis: Because the mRNA re-expression is mainly through the transcriptional regulation in the p...

Among all voltage-gated calcium channels, the T-type Ca2+ channels encoded by the Cav3.2 genes are highly expressed in the hippocampus, which is associated with contextual, temporal and spatial learning and memory. However, the specific involvement of the Cav3.2 T-type Ca2+ channel in these hippocampus-dependent types of learning and memory remains...

Paired-pulse ratio. No significant difference was recorded for paired-pulses ratio of WT (indicated in solid circle) and KO −/− (a1H−/−; indicated in open circle). (TIF)

Raw traces of field excitatory post synaptic potential (fEPSP). No significant difference was observed for raw traces of fEPSP of WT (indicated in solid circle) and KO −/−(a1H−/−; indicated in open circle). (TIF)

TEA-induced fEPSP. No significant difference was observed for TEA-induced fEPSP of WT (indicated in solid circle) and KO −/− (a1H−/−; indicated in open circle). (TIF)

Mice have gained more and more attention in recent years and been widely used in transgenic experiments. Although the number of researches on the heart rate variability (HRV) of mice has been gradually increasing, a consensus on the frequency ranges of autonomic modulation has not been established. Therefore, the main purpose of this study was to f...

Light-evoked responses from vertebrate retinas were recorded as an electroretinogram (ERG). The b-wave is the most prominent component of the ERG, and in the bovine retina its NiCl(2) -sensitive component was attributed to reciprocal signalling by pharmacoresistant R-type voltage-gated Ca(2+) channels, which similar to other voltage-dependent Ca(2+...

Chronic pain is characterized by post-injury pain hypersensitivity. Current evidence suggests that it might result from altered neuronal excitability and/or synaptic functions in pain-related pathways and brain areas, an effect known as central sensitization. Increased activity of extracellular signal-regulated kinase (ERK) has been well-demonstrat...

Mice that have defects in their low-threshold T-type calcium channel (T-channel) genes show altered pain behaviors. The changes in the ratio of nociceptive neurons and the burst firing property of reticular thalamic (RT) and ventroposterior (VP) neurons in Cav3.2 knockout (KO) mice were studied to test the involvement of thalamic T-channel and burs...

Loss of spiral ganglion neurons is a major cause of age-related hearing loss (presbycusis). Despite being the third most prevalent condition afflicting elderly persons, there are no known medications to prevent presbycusis. Because calcium signaling has long been implicated in age-related neuronal death, we investigated T-type calcium channels. Thi...

The T-type calcium channel (T-channel) is a low-voltage-activated channel. Whether T-channels are involved in sympathetic nerve discharge (SND), with subunits α1G and α1H differentially regulating SND genesis, was explored using in vitro brainstem-spinal cord-splanchnic sympathetic nerve preparations of wild-type and genetically modified B6 mice. A...

Application of phorbol 12,13-diacetate (PDA) caused marked enhancement of synaptic transmission of nociceptive parabrachio-amygdaloid (PBA) input onto neurons of the capsular central amygdaloid (CeAC) nucleus. The potentiation of PBA-CeAC EPSCs by PDA involved a presynaptic protein kinase C (PKC)-dependent component and a postsynaptic PKC-extracell...

Although carboplatin is currently used as a therapeutic drug for ovarian, breast, and non-small cell lung cancers, it has serious side effects including renal and cardiac toxicity. Herein, we examined the effect of carboplatin on murine renal tubular cell (RTC) apoptosis both in vivo and in vitro and the underlying molecular mechanisms associated w...

GC (guanylate cyclase)-G is the most recently identified member of the receptor GC family. However, the regulation of its activity and protein expression in the mammalian olfactory system remains unclear. In the present study, we used a GC-G-specific antibody to validate that the GC-G protein is expressed in Grueneberg ganglion neurons, a newly rec...

T‐type calcium channel (T‐channel) is a low‐voltage‐activated channel allowing calcium influx in the voltage range near resting membrane potentials. Functional expression of T‐channel currents only requires alpha1 subunits, including alpha1G, alpha1H, and alpha1I. We investigated whether T‐channel subunits differentially regulate sympathetic tone g...

Under optimal in vitro conditions, isolated spinal cords of neonatal Sprague-Dawley (SD) rats spontaneously generate sympathetic nerve discharge (SND). To aid future studies involving genetically modified mice, we established a preparation to assess SND generation within the mouse spinal cord. Brainstem-spinal cord-splanchnic nerve preparations of...

NMDA receptors play dual and opposing roles in neuronal survival by mediating the activity-dependent neurotrophic signaling and excitotoxic cell death via synaptic and extrasynaptic receptors, respectively. In this study, we demonstrate that the aryl hydrocarbon receptor (AhR), also known as the dioxin receptor, is involved in the expression and th...

In both humans and animals, an insult to the brain can lead, after a variable latent period, to the appearance of spontaneous epileptic seizures that persist for life. The underlying processes, collectively referred to as epileptogenesis, include multiple structural and functional neuronal alterations. We have identified the T-type Ca(2+) channel C...

We constructed a chassis that tightly fixes catheters for cannulation to the muscle. It can buffer pulling forces to avoid a mechanical tearing of the skin of mice as a result of movement. A simple hydraulic swivel was also made for blood pressure recording and drug infusion in freely moving mice.

In the microcirculation, longitudinal conduction of vasomotor responses provides an essential means of coordinating flow distribution among vessels in a complex network. Spread of current along the vessel axis can display a regenerative component, which leads to propagation of vasomotor signals over many millimeters; the ionic basis for the regener...

In spermatozoa, voltage-dependent calcium channels (VDCC) have been involved in different cellular functions like acrosome reaction (AR) and sperm motility. Multiple types of VDCC are present and their relative contribution is still a matter of debate. Based mostly on pharmacological studies, low-voltage-activated calcium channels (LVA-CC), respons...

The aim of this study was to investigate in a transgenic animal model the cardiac expression and function of a novel extracellular protein SCUBE3 [signal peptide-CUB (complement proteins C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor)-like domain-containing protein 3]. Real-time quantitative reverse transcriptase (RT)-PCR analysis showed tha...

It is a tricky task to record electrical signals from the subcutaneous fixed tether assembly in freely moving mouse. The thin and pliable skin of the mouse is easily rent at the sutured incision site by dragging of the external output set during movement. We constructed a light weight chassis that made the output plug-in connector tightly fixed at...

It is a tricky task to record electrical signals from the subcutaneous fixed tether assembly in freely moving mouse. The thin and pliable skin of the mouse is easily rent at the sutured incision site by dragging of the external output set during movement. We constructed a light weight chassis that made the output plug-in connector tightly fixed at...

Although T-type Ca(2+) channels in the thalamus play a crucial role in determining neuronal excitability and are involved in sensory processing and pathophysiology of epilepsy, little is known about the molecular mechanisms involved in their regulation. Here, we report that reducing agents, including endogenous sulfur-containing amino acid l-cystei...

Ca²⁺ channels play critical roles in the regulation of synaptic activity. In contrast to the well established function of voltage-activated Ca²⁺ channels in the presynaptic membrane for neurotransmitter release, some studies are just beginning to elucidate the functions of the Ca²⁺ channels in the postsynaptic membrane. In this study, we demonstrat...

Voltage-dependent calcium channels (VDCC) are multiprotein assemblies that regulate the entry of extracellular calcium into electrically excitable cells and serve as signal transduction centers. The alpha1 subunit forms the membrane pore while the intracellular beta subunit is responsible for trafficking of the channel to the plasma membrane and mo...

Calcium ion (Ca2+) influx through voltage-gated Ca2+ channels is important for the regulation of vascular tone. Activation of L-type Ca2+ channels initiates muscle contraction; however, the role of T-type Ca2+ channels (T-channels) is not clear. We show that mice deficient in the alpha1H T-type Ca2+ channel (alpha(1)3.2-null) have constitutively co...

Muscular dystrophy includes a diverse group of inherited muscle diseases characterized by wasting and weakness of skeletal muscle. Mutations in dysferlin are linked to two clinically distinct muscle diseases, limb-girdle muscular dystrophy type 2B and Miyoshi myopathy, but the mechanism that leads to muscle degeneration is unknown. Dysferlin is a h...

Voltage-gated calcium channels mediate excitationcontraction coupling in the skeletal muscle. Their molecular composition, similar to neuronal channels, includes the pore-forming α1 and auxiliary α2δ, β, and γ subunits. The γ subunits are the least characterized, and their subunit interactions are unclear. The physiological importance of the neuron...

We characterized the neuronal two-domain (95kD-alpha(1)2.1) form of the alpha(1)2.1 subunit of the voltage-gated calcium channels using genetic and molecular analysis. The 95kD-alpha(1)2.1 is absent in neuronal preparations from CACNA1A null mouse demonstrating that alpha(1)2.1 and 95kD-alpha(1)2.1 arise from the same gene. A recombinant two-domain...

A novel gene (Cacng2;γ2 ) encoding a protein similar to the voltage-activated Ca2+ channel γ1 subunit was identified as the defective gene in the epileptic and ataxic mouse, stargazer. In this study, we analyzed the association of this novel neuronal γ2 subunit with Ca2+ channels of rabbit brain, and the function of the γ2 subunit in recombinant ne...

Low voltage-activated, or T-type, calcium currents are important regulators of neuronal and muscle excitability, secretion, and possibly cell growth and differentiation. The gene (or genes) coding for the pore-forming subunit of low voltage-activated channel proteins has not been unequivocally identified. We have used reverse transcription-PCR to i...