According to the analysis and integration on prior research results regarding meridian essence, it is believed that high-energy metabolism is one of the main characteristics of along-meridian specificity. With discussion on the formation mechanism of along-meridians high-energy metabolism as entry point, it is found out that proteins of voltage-gated calcium channel along the meridians are likely to play an essential role of starting and coupling during the along-meridians functional activity. Thus, the hypothesis "proteins coupling in the meridians" is modified to the hypothesis "calcium channels proteins coupling in the meridians", which opens new path to reveal material basis and action mechanism of meridians.
Calcium ; metabolism ; Calcium Channels ; metabolism ; Energy Metabolism ; Humans ; Meridians

Rapamycin (Rap) is an immunosuppressant, which is mainly used in the anti-rejection of organ transplantation. Meanwhile, it also shows great potential in the fields of anticancer, neuroprotection and anti-aging. Rap can inhibit the activity of mammalian target of Rap (mTOR). It activates the transcription factor EB (TFEB) to up-regulate lysosomal function and eliminates the inhibitory effect of mTOR on ULK1 (unc-51 like autophagy activating kinase 1) to promote autophagy. Recent research showed that Rap can directly activate the lysosomal cation channel TRPML1 in an mTOR-independent manner. TRPML1 activation releases lysosomal calcium. Calcineurin functions as the sensor of the lysosomal calcium signal and activates TFEB, thus promoting lysosome function and autophagy. This finding has greatly broadened and deepened our understanding of the pharmacological roles of Rap. In this review, we briefly introduce the canonical Rap-mTOR-ULK1/TFEB signaling pathway, and then discuss the discovery of TRPML1 as a new target of Rap and the pharmacological potential of this novel Rap-TRPML1-Calcineurin-TFEB pathway.
Autophagy ; Calcium/metabolism* ; Calcium Channels ; Lysosomes/metabolism* ; Signal Transduction ; Sirolimus

Transient receptor potential (TRP) ion channels are widely distributed in different kinds of cells. TRP expresses highly in the prostatic cancer epithelia at different levels, but whether it expresses in chronic prostatitis epithelia or not remains poorly understood. Investigating the roles of TRP ion channels in the pathogenesis of prostatic diseases could afford us a new approach to their diagnosis and therapy.
Calcium Channels ; Calcium Signaling ; Humans ; Male ; Prostatic Diseases ; metabolism ; pathology ; Transient Receptor Potential Channels

OBJECTIVETo investigate the mechanism of ethanol-induced calcium overload in hepatocytes and the related role of store-operated calcium channels (SOCs).

METHODSHepG2 cells were treated an ethanol concentration gradient with or without intervention treatment with the extracellular calcium chelator EGTA or the SOCs inhibitor 2-aminoethoxydiphenyl borate (2-APB). Effects on cell viability were assessed by the CCK8 assay. Effects on leakage of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined by automatic biochemical analyzer measurements of the culture supernatants. Effects on cytoplasmic free Ca2+ concentration ([Ca2+]i) were accessed by detecting fluorescence intensity of the calcium indicator Fluo-3/AM with a flow cytometer. Effects on mRNA and protein expression levels of SOCs, stromal interacting factor 1 (STIM1), and calcium release-activated calcium channel protein 1 (Orai1) were evaluated by qPCR and western blotting.

RESULTSThe ethanol treatment produced dose-dependent reduction in cell viability (r = -0.985, P less than 0.01) and increases in leakage of ALT (F = 15.286, P less than 0.01) and AST (F = 39.674, P less than 0.01). Compared to untreated controls, the ethanol treatments of 25, 50, 100, 200 and 400 mM induced significant increases in [Ca2+]i level (1.25+/-0.36, 1.31+/-0.15, 1.41+/-0.18, 2.29+/-0.25, 2.58+/-0.19; F = 15.286, P less than 0.01). Both intervention treatments, EGTA and 2-APB, significantly reduced the 200 mM ethanol treatment-induced [Ca2+]i increase (2.32+/-0.08 reduced to 1.79+/-0.15 (t = 7.201, P less than 0.01) and 1.86+/-0.09 (t = 8.183, P less than 0.01) respectively). EGTA and 2-APB also increased the ethanol-treated cells' viability and reduced the ALT and AST leakage. The 200 mM ethanol treatment stimulated both gene and protein expression of STIM1 and Orai1, and the up-regulation effect lasted at least 72 h after treatment.

CONCLUSIONEthanol-induced dysregulation of SOCs may be an important molecular mechanism of ethanol-induced [Ca2+]i rise in hepatocytes and the related liver cell injury.

Calcium ; metabolism ; Calcium Channels ; metabolism ; Ethanol ; adverse effects ; Hep G2 Cells ; Hepatocytes ; drug effects ; metabolism ; Humans

Autoantibodies ; Calcium Channels ; Humans ; Myasthenia Gravis ; Receptors, Cholinergic/metabolism*

A stochastic model of intracellular calcium oscillations is put forward by taking into account the random opening-closing of Ca2+ channels in endoplasmic reticulum (ER) membrane. The numerical results of the stochastic model show simple and complex calcium oscillations, which accord with the experiment results.
Calcium Channels/*metabolism ; *Calcium Signaling ; Endoplasmic Reticulum/*metabolism ; Intracellular Space ; Kinetics ; Mathematics ; Models, Biological ; Stochastic Processes

Cl(-) channel has been identified in heart over more than a decade. It is now known that Cl(-) channel is a super-family. The potentially important roles of cardiac Cl(-) channels have been emerging. Cardiac Cl(-) channels may play multifunctional roles in both physiological and pathophysiological conditions. Since the existence and distribution of cardiac Cl(-) channels vary with species and cardiac tissues, and blockade of Cl (-) channel with putative Cl(-) channel blockers or Cl(-) substitution has profound influence on cardiac electrical properties, it appears that the main role of cardiac Cl(-) channels may be to modulate cation channels or provide an ionic environment suitable for the activities of cation channels. So, to investigate the relationship between Cl(-) channels and cation channels may be of physiological and pathophysiological significance.
Animals ; Calcium Channels ; physiology ; Cations ; metabolism ; Chloride Channels ; physiology ; Heart ; physiology ; Humans ; Potassium Channels ; physiology ; Sodium Channels ; physiology ; TRPM Cation Channels ; physiology

The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for the past two decades. Store-operated Ca2+-release-activated Ca2+ (CRAC) channels constitute the sole pathway for Ca2+ entry following antigen-receptor engagement. In a set of breakthrough studies over the past two years, stromal interaction molecule 1 (STIM1, the ER Ca2+ sensor) and Orai1 (a pore-forming subunit of the CRAC channel) have been identified. Here we review these recent studies and the insights they provide into the mechanism of store-operated Ca2+ channels (SOCCs).
Animals ; Calcium ; metabolism ; Calcium Channels ; metabolism ; Calcium Signaling ; drug effects ; Humans ; Membrane Proteins ; antagonists & inhibitors ; metabolism ; Protein Binding

The purpose of this study is to identify the electrical activity of neuron, the existence of the transition from bursting pattern to spiking pattern and the ion mechanism of the bursting pattern. The intracellular electrical activity patterns of single neurons in the stomatogastric ganglion (STG) of crayfish were recorded when the extracellular calcium concentration ([Ca(2+)](o)) or calcium-dependent potassium channel blocker tetraethylammonium concentration ([TEA](o)) were changed, using intracellular recording method. These single neurons were also functionally isolated from the ganglion by application of atropine and picrotoxin which could block the inhibitory acetylcholine synapses and glutamatergic synapses respectively. When [Ca(2+)](o) was decreased by increasing EGTA, the membrane potential of the neuron was increased, and the electrical activity patterns were changed from the resting state with lower potential value (resting state of polarization) to the bursting pattern firstly, and then to the spiking pattern, at last to the resting state with higher potential value (resting state of depolarization). When [TEA](o) was increased, the membrane potential of the neuron was increased, and the electrical activity pattern was changed from the resting state with lower potential value (resting state of polarization) to the bursting pattern firstly, and then to the spiking pattern. The duration of the burst of the bursting pattern was increased. When [Ca(2+)](o) was increased or [TEA](o) was decreased, an inverse procedure of the electrical activity pattern was exhibited. On one hand, the results indicate that a single neuron can generate various electrical activity patterns corresponding to different physiological conditions, and the regularity of the transitions between different electrical activity patterns. On the other hand, the results identify that the initiation and termination of the burst in bursting pattern are determined by calcium-activated potassium conductance, which is adjusted by intracellular calcium concentration influenced by inward calcium current. It may be the ionic mechanism of generation of the bursting pattern in a single neuron.
Action Potentials ; physiology ; Animals ; Astacoidea ; physiology ; Calcium ; metabolism ; Calcium Channels ; metabolism ; Ganglia, Invertebrate ; physiology ; Neurons ; physiology ; Potassium Channels, Calcium-Activated ; metabolism

OBJECTIVETo explore the mechanisms of the influx of calcium ions during the activation of ACh-sensitive BK channel (big conductance, calcium-dependent potassium channel) in type II vestibular hair cells of guinea pigs.

METHODSType II vestibular hair cells were isolated by collagenase type IA. Under the whole-cell patch mode, the sensitivity of ACh-sensitive BK current to the calcium channels blockers was investigated, the pharmacological property of L-type calcium channel activator-sensitive current and ACh-sensitive BK current was compared.

RESULTSFollowing application of ACh, type II vestibular hair cells displayed a sustained outward potassium current, with a reversal potential of (-70.5 +/- 10.6) mV (x +/- s, n = 10). At the holding potential of -50 mV, the current amplitude of ACh-sensitive potassium current activated by 100 micromol/L ACh was (267 +/- 106) pA (n = 11). ACh-sensitive potassium current was potently sensitive to the BK current blocker, IBTX (iberiotoxin, 200 nmol/L). Apamin, the well-known small conductance, calcium-dependent potassium current blocker, failed to inhibit the amplitude of ACh-sensitive potassium current at a dose of 1 micromol/L. ACh-sensitive BK current was sensitive to NiCl2 and potently inhibited by CdCl2. NiCl2 and CdCl2 showed a dose-dependent blocking effect with a half inhibition-maximal response of (135.5 +/- 18.5) micromol/L (n = 7) and (23.4 +/- 2.6) micromol/L (n = 7). The L-type calcium channel activator, (-) -Bay-K 8644 (10 micromol /L), mimicked the role of ACh and activated the IBTX-sensitive outward current.

CONCLUSIONACh-sensitive BK and L-type calcium channels are co-located in type II vestibular hair cells of guinea pigs.

Animals ; Calcium Channels, L-Type ; Guinea Pigs ; Hair Cells, Vestibular ; metabolism ; Large-Conductance Calcium-Activated Potassium Channels ; Patch-Clamp Techniques