Attenuation of skeletal muscle atrophy via acupuncture, electro-acupuncture, and electrical stimulation.

Background: Accelerated skeletal muscle wasting is a shared trait among many pathologies and aging. Acupuncture has been used as a therapeutic intervention to control pain; however, little is known about its effects on skeletal muscle atrophy and function. The study's purpose was to compare the effects of acupuncture, electro-acupuncture, and electrical stimulation on cast-induced skeletal muscle atrophy. Methods: Forty female Sprague Dawley rats were randomly divided into groups: Control, casted (CAST), CAST+Acupuncture (CAST-A), 4) CAST+Electro-acupuncture (CAST-EA), and CAST+Electrical stimulation (CAST-ES) (n = 8). Plaster casting material was wrapped around the left hind limb. Acupuncture and electro-acupuncture (10 Hz, 6.4 mA) treatments were applied by needling acupoints (stomach-36 and gallbladder-34). Electrical stimulation (10 Hz, 6.4 mA) was conducted by needling the lateral and medial gastrocnemius muscles. Treatments were conducted for 15 min, three times/week for 14 days. Muscle atrophy F-box (MAFbx), muscle RING finger 1 (MuRF1), and contractile properties were assessed. Results: Fourteen days of cast-immobilization decreased muscle fiber CSA by 56% in the CAST group (p = 0.00); whereas, all treatment groups demonstrated greater muscle fiber CSA than the CAST group (p = 0.00). Cast-immobilization increased MAFbx and MuRF1 protein expression in the CAST group (p<0.01) while the CAST-A, CAST-EA, and CAST-ES groups demonstrated lower levels of MAFbx and MuRF1 protein expression (p<0.02) compared to the CAST group. Following fourteen days of cast-immobilization, peak twitch tension did not differ between the CAST-A and CON groups (p = 0.12). Conclusion: Skeletal muscle atrophy, induced by 14 days of cast-immobilization, was significantly attenuated by acupuncture, electro-acupuncture, or electrical stimulation.

Disparities in Short-Term Depression Among Prefrontal Cortex Synapses Sustain Persistent Activity in a Balanced Network.

Persistent activity of cue-representing neurons in the prefrontal cortex (PFC) is regarded as a neural basis for working memory. The contribution of short-term synaptic plasticity (STP) at different types of synapses comprising the cortical network to persistent activity, however, remains unclear. Characterizing STP at synapses of the rat PFC layer 5 network, we found that PFC synapses exhibit distinct STP patterns according to presynaptic and postsynaptic identities. Excitatory postsynaptic currents (EPSCs) from corticopontine (Cpn) neurons were well sustained throughout continued activity, with stronger depression at synapses onto fast-spiking interneurons than those onto pyramidal cells. Inhibitory postsynaptic currents (IPSCs) were sustained at a weaker level compared with EPSC from Cpn synapses. Computational modeling of a balanced network incorporating empirically observed STP revealed that little depression at recurrent excitatory synapses, combined with stronger depression at other synapses, could provide the PFC with a unique synaptic mechanism for the generation and maintenance of persistent activity.

Intracellular Zn2+ Signaling Facilitates Mossy Fiber Input-Induced Heterosynaptic Potentiation of Direct Cortical Inputs in Hippocampal CA3 Pyramidal Cells.

Repetitive action potentials (APs) in hippocampal CA3 pyramidal cells (CA3-PCs) backpropagate to distal apical dendrites, and induce calcium and protein tyrosine kinase (PTK)-dependent downregulation of Kv1.2, resulting in long-term potentiation of direct cortical inputs and intrinsic excitability (LTP-IE). When APs were elicited by direct somatic stimulation of CA3-PCs from rodents of either sex, only a narrow window of distal dendritic [Ca2+] allowed LTP-IE because of Ca2+-dependent coactivation of PTK and protein tyrosine phosphatase (PTP), which renders non-mossy fiber (MF) inputs incompetent in LTP-IE induction. High-frequency MF inputs, however, could induce LTP-IE at high dendritic [Ca2+] of the window. We show that MF input-induced Zn2+ signaling inhibits postsynaptic PTP, and thus enables MF inputs to induce LTP-IE at a wide range of [Ca2+]i values. Extracellular chelation of Zn2+ or genetic deletion of vesicular zinc transporter abrogated the privilege of MF inputs for LTP-IE induction. Moreover, the incompetence of somatic stimulation was rescued by the inhibition of PTP or a supplement of extracellular zinc, indicating that MF input-induced increase in dendritic [Zn2+] facilitates the induction of LTP-IE by inhibiting PTP. Consistently, high-frequency MF stimulation induced immediate and delayed elevations of [Zn2+] at proximal and distal dendrites, respectively. These results indicate that MF inputs are uniquely linked to the regulation of direct cortical inputs owing to synaptic Zn2+ signaling.SIGNIFICANCE STATEMENT Zn2+ has been mostly implicated in pathological processes, and the physiological roles of synaptically released Zn2+ in intracellular signaling are little known. We show here that Zn2+ released from hippocampal mossy fiber (MF) terminals enters postsynaptic CA3 pyramidal cells, and plays a facilitating role in MF input-induced heterosynaptic potentiation of perforant path (PP) synaptic inputs through long-term potentiation of intrinsic excitability (LTP-IE). We show that the window of cytosolic [Ca2+] that induces LTP-IE is normally very narrow because of the Ca2+-dependent coactivation of antagonistic signaling pairs, whereby non-MF inputs become ineffective in inducing excitability change. The MF-induced Zn2+ signaling, however, biases toward facilitating the induction of LTP-IE. The present study elucidates why MF inputs are more privileged for the regulation of PP synapses.

Vitamin D3 Supplementation Reduces the Symptoms of Upper Respiratory Tract Infection during Winter Training in Vitamin D-Insufficient Taekwondo Athletes: A Randomized Controlled Trial.

Vitamin D insufficiency may be associated with increased risk of upper respiratory tract infection (URTI) in athletes. This study examined the effects of vitamin D3 supplementation on salivary immune functions and symptoms of URTI in vitamin D-insufficient taekwondo athletes. Twenty-five male taekwondo athletes, aged 19⁻22 years with vitamin D insufficiency [serum 25-hydroxyvitamin-D concentrations (25(OH)D, 31.3 ± 1.39 nmol/L)], participated in this study. They were randomized to receive 5000 IU/day of vitamin D3 (n = 13) or placebo capsule (n = 12) during 4 weeks of winter training. Blood samples were collected two times (pre- and post-tests) for analyzing serum 25(OH)D concentration while salivary samples were obtained three times (pre-, mid-, and post-tests) for secretory immunoglobulin A (SIgA) and lactoferrin analyses. The symptoms of URTI were reported daily during the intervention. Serum 25(OH)D concentration significantly increased by 255.6% in the vitamin D group, whereas in the placebo group it did not change (p < 0.001). While the significant increase in SIgA was observed in both groups (p < 0.001), elevated salivary lactoferrin level in response to winter training was found only in the placebo group (p = 0.011). The change in serum 25(OH)D concentration was negatively associated with total URTI symptoms (r = -0.435, p = 0.015). Vitamin D3 supplementation may be effective in reducing the symptoms of URTI during winter training in vitamin D-insufficient taekwondo athletes.

Correcting Vitamin D Insufficiency Improves Some But Not All Aspects of Physical Performance During Winter Training in Taekwondo Athletes.

We investigated the effects of vitamin D3 supplementation on physical performance during winter training in vitamin D insufficient taekwondo athletes. Thirty-five collegiate male and female taekwondo athletes, aged 19-22 years with low serum 25(OH)D concentration (28.8 ± 1.10 nmol/L), were randomly assigned to a vitamin D group (n = 20) or a placebo group (n = 15). Subjects received either a vitamin D3 capsule (5,000 IU/day) or a placebo during 4 weeks of winter training. Blood samples were collected for analyzing serum 25(OH)D concentration. Physical performance tests included Wingate anaerobic test, isokinetic muscle strength and endurance, a countermovement jump test, sit-ups, agility test, and 20-m pacer. Serum 25(OH)D concentrations increased significantly in the vitamin D group (96.0 ± 3.77 nmol/L) after 4 weeks of supplementation, but no changes were found in the placebo group (F = 242.44, p = .000). There were significant interaction effects for anaerobic peak power (F = 7.49, p = .010) and isokinetic knee extension at 180 deg/s (F = 6.08, p = .019). Changes in serum 25(OH)D concentration were positively associated with changes in peak power and isokinetic knee extension at 180 deg/s. However, no significant interaction effects were observed in other performance variables. This study suggests that 4 weeks of vitamin D supplementation elevates serum 25(OH)D concentration to sufficient levels. Correcting vitamin D insufficiency improves some but not all aspects of performance. Thus, efficacy of vitamin D supplementation to enhance performance remains unclear.

Interaction of resistance training, electroacupuncture and Huang Qi supplementation on skeletal muscle function and GLUT4 protein concentration in rats.

OBJECTIVE: To determine the effects and potential synergy of resistance training (RT), Huang Qi (HQ) herbal supplementation, and electroacupuncture (EA) on skeletal muscle mass, contractile properties, and components of the insulin signalling pathway in healthy Sprague Dawley rats. METHODS: Female Sprague Dawley rats were randomly assigned to one of five groups (n=8 each): control (CON), RT only, RT with EA (RT-EA), RT with HQ (RT-HQ), and RT combined with both EA and HQ (RT-EA-HQ). RT was performed using ladder climbing every other day for 8 weeks. Sparse-wave EA was applied for 15 min/day, 3 times/week for 8 weeks. HQ supplementation was provided via oral gavage daily for 8 weeks. RESULTS: RT significantly increased the muscle mass of the flexor hallucis longus (FHL) compared to CON. The isometric twitch and tetanic tension of the FHL in the RT-EA, RT-HQ, and RT-EA-HQ groups were significantly higher compared to CON and RT groups. RT-EA treatment (with or without HQ) significantly increased GLUT4 protein concentration but had no impact on Akt-2. CONCLUSIONS: EA appears to be an effective treatment modality for increasing muscle mass and function when combined with RT. RT-EA may also be an effective method for improving glucose tolerance as a result of increases in GLUT4 protein concentration.

Analysis of Chameleonic Change of Red Cabbage Depending on Broad pH Range for Dye-Sensitized Solar Cells.

Dye-sensitized solar cells (DSSCs) were assembled using natural dyes extracted from red cabbage as a sensitizer. In this work, we investigated the adsorption characteristics and the electrochemical behavior for harvesting sunlight and electron transfer in red cabbage DSSCs under different solvents and pH. For the red cabbage dye-sensitized electrode adsorbed at pH 3.5, the solar cell yields a short-circuit current density (Jsc) of 1.60 mA/cm2, a photovoltage (Vcc) of 0.46 V, and a fill factor of 0.55, corresponding to an energy conversion efficiency (η) of 0.41%.

Influence of polar solvents on photovoltaic performance of Monascusred dye-sensitized solar cell.

Dye-sensitized solar cells (DSSCs) were assembled using natural dyes extracted from Monascus red pigment as a sensitizer. In this work, we studied the adsorption characteristics for harvesting sunlight and the electrochemical behavior for electron transfer in Monascus red DSSC using different solvents. The effect of polar aprotic and protic solvents including water, ethanol, and dimethylsulfoxide (DMSO) used in the sensitization process was investigated for the improvement in conversion efficiency of a cell. As for the Monascus red dye-sensitized electrode in DMSO solvent, the solar cell yields a short-circuit current density (Jsc) of 1.23mA/cm(2), a photovoltage (Voc) of 0.75V, and a fill factor of 0.72, corresponding to an energy conversion efficiency (η) of 0.66%.

Post-tetanic increase in the fast-releasing synaptic vesicle pool at the expense of the slowly releasing pool.

Post-tetanic potentiation (PTP) at the calyx of Held synapse is caused by increases not only in release probability (P(r)) but also in the readily releasable pool size estimated from a cumulative plot of excitatory post-synaptic current amplitudes (RRP(cum)), which contribute to the augmentation phase and the late phase of PTP, respectively. The vesicle pool dynamics underlying the latter has not been investigated, because PTP is abolished by presynaptic whole-cell patch clamp. We found that supplement of recombinant calmodulin to the presynaptic pipette solution rescued the increase in the RRP(cum) after high-frequency stimulation (100 Hz for 4-s duration, HFS), but not the increase in P(r). Release-competent synaptic vesicles (SVs) are heterogeneous in their releasing kinetics. To investigate post-tetanic changes of fast and slowly releasing SV pool (FRP and SRP) sizes, we estimated quantal release rates before and 40 s after HFS using the deconvolution method. After HFS, the FRP size increased by 19.1% and the SRP size decreased by 25.4%, whereas the sum of FRP and SRP sizes did not increase. Similar changes in the RRP were induced by a single long depolarizing pulse (100 ms). The post-tetanic complementary changes of FRP and SRP sizes were abolished by inhibitors of myosin II or myosin light chain kinase. The post-tetanic increase in the FRP size coupled to a decrease in the SRP size provides the first line of evidence for the idea that a slowly releasing SV can be converted to a fast releasing one.

Dimethyl lithospermate B, an extract of Danshen, suppresses arrhythmogenesis associated with the Brugada syndrome.

BACKGROUND: Dimethyl lithospermate B (dmLSB) is an extract of Danshen, a traditional Chinese herbal remedy, which slows inactivation of INa, leading to increased inward current during the early phases of the action potential (AP). We hypothesized that this action would be antiarrhythmic in the setting of Brugada syndrome. METHODS AND RESULTS: The Brugada syndrome phenotype was created in canine arterially perfused right ventricular wedge preparations with the use of either terfenadine or verapamil to inhibit INa and ICa or pinacidil to activate IK-ATP. AP recordings were simultaneously recorded from epicardial and endocardial sites together with an ECG. Terfenadine, verapamil, and pinacidil each induced all-or-none repolarization at some epicardial sites but not others, leading to ST-segment elevation as well as an increase in both epicardial and transmural dispersions of repolarization (EDR and TDR, respectively) from 12.9+/-9.6 to 107.0+/-54.8 ms and from 22.4+/-8.1 to 82.2+/-37.4 ms, respectively (P<0.05; n=9). Under these conditions, phase 2 reentry developed as the epicardial AP dome propagated from sites where it was maintained to sites at which it was lost, generating closely coupled extrasystoles and ventricular tachycardia and fibrillation. Addition of dmLSB (10 micromol/L) to the coronary perfusate restored the epicardial AP dome, reduced EDR and TDR to 12.4+/-18.1 and 24.4+/-26.7 ms, respectively (P<0.05; n=9), and abolished phase 2 reentry-induced extrasystoles and ventricular tachycardia and fibrillation in 9 of 9 preparations. CONCLUSIONS: Our data suggest that dmLSB is effective in eliminating the arrhythmogenic substrate responsible for the Brugada syndrome and that it deserves further study as a pharmacological adjunct to implanted cardioverter/defibrillator usage.

A novel Na+ channel agonist, dimethyl lithospermate B, slows Na+ current inactivation and increases action potential duration in isolated rat ventricular myocytes.

Voltage-gated Na(+) channel blockers have been widely used as local anaesthetics and antiarrhythmic agents. It has recently been proposed that Na(+) channel agonists can be used as inotropic agents. Here, we report the identification of a natural substance that acts as a Na(+) channel agonist. Using the patch-clamp technique in isolated rat ventricular myocytes, we investigated the electrophysiological effects of the substances isolated from the root extract of Salvia miltiorrhiza, which is known as 'Danshen' in Asian traditional medicine. By the intensive activity-guided fractionation, we identified dimethyl lithospermate B (dmLSB) as the most active component, while LSB, which is the major component of the extract, showed negligible electrophysiological effect. Action potential duration (APD(90)) was increased by 20 microM dmLSB from 58.8 +/- 12.1 to 202.3 +/- 9.5 ms. In spite of the prolonged APD, no early after-depolarization (EAD) was observed. dmLSB had no noticeable effect on K(+) or Ca(2+) currents, but selectively affected Na(+) currents (I(Na)). dmLSB slowed the inactivation kinetics of I(Na) by increasing the proportion of slowly inactivating component without inducing any persistent I(Na). The relative amplitude of slow component compared to the peak fast I(Na) was increased dose dependently by dmLSB (EC(50) = 20 microM). Voltage dependence of inactivation was not affected by dmLSB, while voltage dependence of activation shifted by 5 mV to the depolarised direction. Since the APD prolongation by dmLSB did not provoke EAD, which is thought as a possible mechanism for the proarrhythmia seen in other Na(+) channel agonists, dmLSB might be an excellent candidate for a Na(+) channel agonist.

K+-dependent Na+/Ca2+ exchange is a major Ca2+ clearance mechanism in axon terminals of rat neurohypophysis.

Two different families of Na+/Ca2+ exchangers, K+-independent NCX and K+-dependent NCKX, are known. Exploiting the outward K+ gradient, NCKX is able to extrude Ca2+ more efficiently than NCX, even when the Na+ gradient is reduced. The NCKX, which was originally thought to be limited to the retinal photoreceptor, was shown recently to be widely distributed in the brain. We investigated the contribution of Na+/Ca2+ exchange to Ca2+ clearance mechanisms in neurohypophysial (NHP) axon terminals, using patch-clamp and microfluorometry techniques. In the presence of internal K+, Ca2+ decay was significantly slowed by the removal of external Na+, indicative of the role of Na+/Ca2+ exchange. As internal [K+] was decreased, Ca2+ decay rate and its dependence on Na+ were greatly attenuated. In the absence of internal K+, Ca2+ decay rate was little affected by Na+ removal. Quantitative analysis using Ca2+ decay rate constant indicated that >60% of Ca2+ extrusion is mediated by Na+/Ca2+ exchange when peak [Ca2+] level is higher than 500 nm, and approximately 90% of Na+/Ca2+ exchange activity is K+ dependent. In situ hybridization confirmed the expression of NCKX2 transcripts in the supraoptic nucleus in which soma of NHP axon terminals are located. To our knowledge, this is the first report to show the significant role of K+-dependent Na+/Ca2+ exchange in neuronal cells other than photoreceptors. Considering that axon terminals are subject to an invasion by high-frequency Na+ spikes, which may lower Na+ gradients, the presence of NCKX may have a functional significance in intracellular Ca2+ regulation.