Recently, more and more studies have discovered that some diseases result from gene defect and functional variation of ion channels, which are called ion passage diseases or ion channelopathies. Meanwhile, it has been found that even though many diseases do not fall into the category of the ion passage disease, some links or passages during the disease development are closely related with the malfunction of ion channels, and many drugs can prevent and cure these diseases by acting on ion channels. Therefore, the relationship between physiology/pathophysiology and ion channels is gradually becoming one of the hot topics in the current researches. The recent progress in the researches on the relationship between penile erection and ion channels is briefly reviewed in this article.
Calcium Channels ; physiology ; Chloride Channels ; physiology ; Connexin 43 ; genetics ; Erectile Dysfunction ; etiology ; Humans ; Ion Channels ; physiology ; Male ; Penile Erection ; physiology ; Potassium Channels ; physiology

Despite a few genes that do not encode ion channels have been identified as implicating some kinds of human idiopathic epilepsies(IE) in recent years, but genetic discoveries have shown the ion channels to play a central role in genetic pathomechanism of IE. The gene mutations of ion channels are a common cause of some rare monogenic IE which could be so-called as channelopathies, and able to be applied to account for the questioned epileptic syndrome to minority of families and sporadic cases. However, more frustrating has been from the genetic research on more common IE with complex inheritance due to the unknown mode of inheritance, the phenotypic heterogeneity and the uncertainty of genetic overlap among syndrome subtypes, which have limited gene mapping. Absence epilepsy is a kind of common IE subtype and shows a complex way to inherit. Evidences from heredity investigation indicate that eleven genes are correlated with absence epilepsy, of which four encode the neuronal calcium channel subunits. Therefore, calcium channel genes may be considered as important candidates for involving in absence epilepsy. To focus the genetics research on calcium channel genes of absence epilepsy may be opening an optimal gate to the pathogenetic study of more common IE with complex inheritance, and benefit to elucidate the molecular mechanisms of absence epilepsy finally, one of the more common IE subtypes with complex inheritance.
Calcium ; metabolism ; Calcium Channels ; genetics ; physiology ; Epilepsy, Absence ; genetics ; physiopathology ; Genetic Predisposition to Disease ; genetics ; Humans ; Models, Biological

OBJECTIVETo observe the effect of Maixinkang Capsule (MXK) on Ca2t concentration and mitochondrial membrane potential in liver cells of ApoE(-/-) mice.

METHODSLiver cells from ApoE(-/-) mice were separated using collagenase digestive method. After the primary cells were cultured for 8 days in vitro, the concentration of 10% MXK contained rat's serum was added into the culture fluid. The Ca2+ concentration and mitochondrial membrane potential in liver cells after 48-hr culture were measured by confocal laser scanning microscopy with Flou-3 and Jc-1 as probes.

RESULTSMXK could decrease Ca2+ concentration in liver cells, which was significantly different to that in the control group (P < 0.01). Meanwhile, MXK could significantly improve mitochondrial membrane potential in liver cells (P < 0.01). There was no obvious dose-effect relationship shown in both effects of MXK.

CONCLUSIONMXK can decrease Ca2+ concentration and improve the mitochondrial membrane potential in liver cells of ApoE(-/-) mice so as to regulate the lipids and prevent the occurrence and development of hyperlipemia and atherosclerosis.

Animals ; Animals, Newborn ; Apolipoproteins E ; genetics ; Calcium Channels ; drug effects ; Hepatocytes ; physiology ; Membrane Potentials ; Mice ; Mice, Knockout ; Mitochondrial Membranes ; physiology

A growing body of evidence, including studies using genetically engineered mouse models, has shown that Ca2+ cycling and Ca2+ -dependent signaling pathways play a pivotal role in cardiac hypertrophy and heart failure. In addition, recent studies identified that mutations of the genes encoding sarcoplasmic reticulum (SR) proteins cause human cardiomyopathies and lethal ventricular arrhythmias. The regulation of Ca2+ homeostasis via the SR proteins may have potential therapeutic value for heart diseases such as cardiomyopathy, heart failure and arrhythmias.
Animals ; Animals, Genetically Modified ; Arrhythmia/genetics ; Calcium/*metabolism ; Calcium Channels/genetics/*physiology ; Calcium-Binding Proteins/genetics/*physiology ; Cardiac Output, Low/genetics ; Cardiomyopathies/genetics ; Heart Diseases/*etiology/genetics/metabolism ; Humans ; Mutation/genetics ; Research Support, Non-U.S. Gov't ; Sarcoplasmic Reticulum/metabolism

The mRNA and protein expression of skeletal dihydropyridine receptor isoform alpha1 subunit (DHPR(alpha1)) and ryanodine receptor(1-3) (RyR(1-3)) during chronic electrical stimulation (CES) of phrenic nerve have rarely been explored. In the present study, we explored the signal translation mode of calcium release unit in diaphragm muscle of rabbits after CES. Thirty rabbits were used and randomly divided into the normal, 10, 20, 50 and 100 Hz groups. Phrenic nerve was continuously (5 weeks, 2x 2 h/d) stimulated at 10, 20, 50 and 100 Hz respectively (impulse width 0.2 ms, 3~6 waves/time, 45 times/min, 10~20 V). Reverse transcription PCR and immunohistochemical methods were employed. The results showed that mRNA and protein expressions of DHPR(alpha1) and RyR(1) in 10 and 20 Hz groups were more significantly lower than those in the control group (P<0.01), but mRNA and protein expressions of DHPR(alpha1) and RyR(1) were significantly higher in 50 and 100 Hz groups than those in the control group (P<0.01); a lower level of mRNA expression of RyR(2) was found in 10 and 20 Hz groups. It is suggested that the calcium release unit and the signal transduction mode between DHPR and RyRs were altered from conformational changes of linked proteins to Ca(2+)-induced Ca(2+) release (CICR) in the diaphragmatic muscle of rabbits after chronic low-frequency electrical stimulation of phrenic nerve for 5 weeks.
Animals ; Calcium ; metabolism ; Calcium Channels, L-Type ; biosynthesis ; genetics ; Diaphragm ; metabolism ; physiology ; Electric Stimulation ; Female ; Male ; Muscle, Skeletal ; metabolism ; physiology ; Phrenic Nerve ; metabolism ; physiology ; RNA, Messenger ; biosynthesis ; genetics ; Rabbits ; Random Allocation ; Ryanodine Receptor Calcium Release Channel ; biosynthesis ; genetics

In Candida albicans, adaptation to environmental pH is relevant to its pathogenicity. Calcium signaling pathway involves in many stress responses and often accompany with Ca2+ fluctuation. We constructed CCH1 and MID1 mutant strains and studied their effect on calcium influx and further investigated the regulation by Crz1p transcription factor. We used PCR-directed gene disruption to construct cch1delta/delta and mid1delta/delta null mutant. By using a flow cytometry-based method we monitored the free cytosolic Ca2+ levels under alkaline stress. Moreover, we constructed pPHO89-LacZ plasmids and by beta-Galactosidase assays, we analyzed the changes of LacZ activities after gene disruption. The results showed that alkaline stress induced calcium burst reduced obviously in cch1delta/delta and mid1delta/delta mutant strains, also for LacZ activities, and fully abolished in crz1delta/delta mutant strain. Finally, by realtime PCR, we confirmed the regulation role of Crz1p in CCH1 and MID1 genes but in a calcineurin independent way. Studies on the effect of calcium pathway on response to alkaline stress will provide an important theoretical basis for Candida albicans infection-oriented treatment and new drug targets.
Calcium Channels ; metabolism ; Candida albicans ; genetics ; metabolism ; physiology ; Fungal Proteins ; genetics ; physiology ; Gene Expression Regulation, Fungal ; Hydrogen-Ion Concentration ; Signal Transduction ; Stress, Physiological ; Transcription Factors ; metabolism ; physiology

No abstract available.
Animal ; Calcium Channels/physiology* ; Calcium Channels/chemistry ; Gene Expression Regulation ; Human ; Ion Channel Gating/physiology* ; Mice ; Mutation ; Nervous System/metabolism ; Nervous System Diseases/physiopathology ; Nervous System Diseases/genetics ; Neurons/physiology*

The present study was aimed to investigate the effect of Janus kinase 3 (JAK3) on the migration of breast cancer cells and the underlying mechanism. The expression of JAK3 in breast cancer MCF-7 cells was silenced by siRNA (siJAK3). The migration ability of MCF-7 cells was detected by scratch test. The activity of store-operated calcium channel (SOCC) was detected by fluorescence calcium imaging. The expression levels of Orai1 and STIM1, key molecules in the process of store-operated calcium entry (SOCE) were detected by Western blot and RT-PCR. The results showed that 2-APB, an inhibitor of SOCC, could inhibit the migration ability of MCF-7 cells. siJAK3 transfection significantly inhibited the migration ability of MCF-7 cells, decreased the activity of SOCC, and down-regulated mRNA and protein expression levels of Orai1 and Stim1. Over-expression of Orai1 or STIM1 in JAK3-silenced cells restored their migration ability. These results suggest that JAK3 facilitates the migration of breast cancer cells by SOCC.
Breast Neoplasms ; enzymology ; Calcium ; metabolism ; Calcium Channels ; metabolism ; Cell Movement ; physiology ; Gene Expression Regulation, Neoplastic ; Humans ; Janus Kinase 3 ; genetics ; metabolism ; MCF-7 Cells ; ORAI1 Protein ; genetics

During membrane depolarization associated with skeletal excitation-contraction (EC) coupling, dihydropyridine receptor [DHPR, a L-type Ca2+ channel in the transverse (t)-tubule membrane] undergoes conformational changes that are transmitted to ryanodine receptor 1 [RyR1, an internal Ca2+-release channel in the sarcoplasmic reticulum (SR) membrane] causing Ca2+ release from the SR. Canonical-type transient receptor potential cation channel 3 (TRPC3), an extracellular Ca2+-entry channel in the t-tubule and plasma membrane, is required for full-gain of skeletal EC coupling. To examine additional role(s) for TRPC3 in skeletal muscle other than mediation of EC coupling, in the present study, we created a stable myoblast line with reduced TRPC3 expression and without alpha1SDHPR (MDG/TRPC3 KD myoblast) by knock-down of TRPC3 in alpha1SDHPR-null muscular dysgenic (MDG) myoblasts using retrovirus-delivered small interference RNAs in order to eliminate any DHPR-associated EC coupling-related events. Unlike wild-type or alpha1SDHPR-null MDG myoblasts, MDG/TRPC3 KD myoblasts exhibited dramatic changes in cellular morphology (e.g., unusual expansion of both cell volume and the plasma membrane, and multi-nuclei) and failed to differentiate into myotubes possibly due to increased Ca2+ content in the SR. These results suggest that TRPC3 plays an important role in the maintenance of skeletal muscle myoblasts and myotubes.
Animals ; Calcium/metabolism ; Calcium Channels/metabolism ; Calcium Channels, L-Type/genetics/metabolism ; Cations/metabolism ; *Cell Differentiation ; *Cell Proliferation ; Cells, Cultured ; Excitation Contraction Coupling ; Gene Knockdown Techniques ; Membrane Potentials ; Mice ; Muscle Fibers, Skeletal/*metabolism ; Muscle Proteins/metabolism ; Myoblasts, Skeletal/*metabolism ; Ryanodine Receptor Calcium Release Channel/metabolism ; Sarcoplasmic Reticulum/*physiology ; Synaptophysin/metabolism ; TRPC Cation Channels/genetics/*metabolism ; Transient Receptor Potential Channels/metabolism

Transient receptor potential (TRP) A1, a member of TRP channel family, is activated by noxious cold. The aims of this study were to determine if TRPA1 contributed to cold-induced contractions in the isolated rat colon preparations and explore the potential mechanisms. The colon smooth muscle layers were surgically isolated from the male Wistar rats and changes in isotonic tension of longitudinal muscle under various treatments were recorded as colonic motilities. Cold stimuli were obtained by the reperfusion with Krebs-Henseleit solution at given temperature using Constant Flow Pump. The mRNA expressions of TRPA1, TRPV1 and TRPM8 in rat colon smooth muscle layer were examined by using reverse transcription-polymerase chain reaction (RT-PCR) techniques. The results showed that the contractions induced by cold stimuli (from 37 degrees C to 12 degrees C stepwise) were inversely proportional to the temperature with a maximum contraction at 17 degrees C in both proximal and distal colons (P<0.01). RT-PCR analysis revealed the expression of TRPA1, but not TRPM8 and TRPV1, in the rat proximal and distal colon smooth muscle layers. Cold-induced colonic contractions were specially inhibited by TRPA1 blocker, ruthenium red (30 μmol/L), in the proximal and distal colon (P<0.05). The cold-induced contractions of proximal (P<0.01, P<0.05) and distal colons (both P<0.001) were almost abolished or inhibited by the pretreatments of TRPA1 agonists, Allyl isothiocyanate (AITC, 300 μmol/L) and cinnamaldehyde (CA, 1 mmol/L). Extracellular calcium removal (EGTA, 1 mmol/L), PLC blocker (U73122, 10 μmol/L) and IP(3) receptor blocker (2-aminoethoxydiphenyl borate, 2-APB, 30 μmol/L) all decreased the contractions evoked by the cooling at 17 degrees C in the proximal and distal colon (P<0.001, P<0.05, P<0.001). Atropine (1 μmol/L) had no effects on these contractions. L-type Ca(2+) channels blocker nifedipine (1 μmol/L) and neurotoxin tetrodotoxin (TTX, 2 μmol/L) decreased the contractile response in the distal colon (P<0.01, P<0.05), but not in the proximal colon. In conclusion, TRPA1 contributes to cold-induced contractions of the rat colon smooth muscle, and the mechanism of TRPA1 activation involves PLC/IP(3)/Ca(2+) pathway. L-type Ca(2+) channel and neurogenic mechanism other than muscarinic receptor might be partially involved in cold-induced contraction of the distal colon, which probably resulted in higher contraction of distal colon compared with that of proximal colon.
Animals ; Calcium Channels, L-Type ; metabolism ; Cold Temperature ; Colon ; metabolism ; physiology ; In Vitro Techniques ; Male ; Muscle Contraction ; physiology ; Muscle, Smooth ; metabolism ; physiology ; Physical Stimulation ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; TRPA1 Cation Channel ; TRPC Cation Channels ; genetics ; metabolism