Skeletal muscle mitoflashes, pH, and the role of uncoupling protein-3.

Mitochondrial reactive oxygen species (ROS) are important cellular signaling molecules, but can cause oxidative damage if not kept within tolerable limits. An important proximal form of ROS in mitochondria is superoxide. Its production is thought to occur in regulated stochastic bursts, but current methods using mitochondrial targeted cpYFP to assess superoxide flashes are confounded by changes in pH. Accordingly, these flashes are generally referred to as 'mitoflashes'. Here we provide regulatory insights into mitoflashes and pH fluctuations in skeletal muscle, and the role of uncoupling protein-3 (UCP3). Using quantitative confocal microscopy of mitoflashes in intact muscle fibers, we show that the mitoflash magnitude significantly correlates with the degree of mitochondrial inner membrane depolarization and ablation of UCP3 did not affect this correlation. We assessed the effects of the absence of UCP3 on mitoflash activity in intact skeletal muscle fibers, and found no effects on mitoflash frequency, amplitude or duration, with a slight reduction in the average size of mitoflashes. We further investigated the regulation of pH flashes (pHlashes, presumably a component of mitoflash) by UCP3 using mitochondrial targeted SypHer (mt-SypHer) in skeletal muscle fibers. The frequency of pHlashes was significantly reduced in the absence of UCP3, without changes in other flash properties. ROS scavenger, tiron, did not alter pHlash frequency in either WT or UCP3KO mice. High resolution respirometry revealed that in the absence of UCP3 there is impaired proton leak and Complex I-driven respiration and maximal coupled respiration. Total cellular production of hydrogen peroxide (H2O2) as detected by Amplex-UltraRed was unaffected. Altogether, we demonstrate a correlation between mitochondrial membrane potential and mitoflash magnitude in skeletal muscle fibers that is independent of UCP3, and a role for UCP3 in the control of pHlash frequency and of proton leak- and Complex I coupled-respiration in skeletal muscle fibers. The differential regulation of mitoflashes and pHlashes by UCP3 and tiron also indicate that the two events, though may be related, are not identical events.

Purinergic Signaling Modulates Survival/Proliferation of Human Dental Pulp Stem Cells.

Human dental pulp stem cells (hDPSCs) reside in postnatal dental pulp and exhibit the potential to differentiate into odontoblasts as well as neurons. However, the intercellular signaling niches necessary for hDPSC survival and self-renewal remain largely unknown. The objective of this study is to demonstrate the existence of intercellular purinergic signaling in hDPSCs and to assess the impact of purinergic signaling on hDPSC survival and proliferation. hDPSCs were isolated from extracted third molars and cultured in minimum essential medium. To demonstrate responsiveness to ATP application and inhibitions by purinergic receptor antagonists, whole cell patch-clamp recordings of ATP-induced currents were recorded from cultured hDPSCs. Immunofluorescence and enzymatic histochemistry staining were performed to assess purinergic receptor expression and ectonucleotidase activity in hDPSCs, respectively. To determine the effects of purinergic signaling on hDPSC, purinergic receptor antagonists and an ectonucleotidase inhibitor were applied in culture medium, and hDPSC survival and proliferation were assessed with DAPI staining and Ki67 immunofluorescence staining, respectively. We demonstrated that ATP application induced inward currents in hDPSCs. P2X and P2Y receptors are involved in the generation of ATP-induced inward currents. We also detected expression of NTPDase3 and ectonucleotidase activity in hDPSCs. We further demonstrated that purinergic receptors were tonically activated in hDPSCs and that inhibition of ectonucleotidase activity enhanced ATP-induced inward currents. Furthermore, we found that blocking P2Y and P2X receptors reduced-and inhibition of ecto-ATPase activity enhanced-the survival and proliferation of hDPSCs, while blocking P2X receptors alone affected only hDPSC proliferation. Autocrine/paracrine purinergic signaling is essential for hDPSC survival and proliferation. These results reveal potential targets to manipulate hDPSCs to promote tooth/dental pulp repair and regeneration.

CD73 Controls Extracellular Adenosine Generation in the Trigeminal Nociceptive Nerves.

Purinergic signaling is involved in pain generation and modulation in the nociceptive sensory nervous system. Adenosine triphosphate (ATP) induces pain via activation of ionotropic P2X receptors while adenosine mediates analgesia via activation of metabotropic P1 receptors. These purinergic signaling are determined by ecto-nucleotidases that control ATP degradation and adenosine generation. Using enzymatic histochemistry, we detected ecto-AMPase activity in dental pulp, trigeminal ganglia (TG) neurons, and their nerve fibers. Using immunofluorescence staining, we confirmed the expression of ecto-5'-nucleotidase (CD73) in trigeminal nociceptive neurons and their axonal fibers, including the nociceptive nerve fibers projecting into the brainstem. In addition, we detected the existence of CD73 and ecto-AMPase activity in the nociceptive lamina of the trigeminal subnucleus caudalis (TSNC) in the brainstem. Furthermore, we demonstrated that incubation with specific anti-CD73 serum significantly reduced the ecto-AMPase activity in the nociceptive lamina in the brainstem. Our results indicate that CD73 might participate in nociceptive modulation by affecting extracellular adenosine generation in the trigeminal nociceptive pathway. Disruption of TG neuronal ecto-nucleotidase expression and axonal terminal localization under certain circumstances such as chronic inflammation, oxidant stress, local constriction, and injury in trigeminal nerves may contribute to the pathogenesis of orofacial neuropathic pain.

External Dentin Stimulation Induces ATP Release in Human Teeth.

ATP is involved in neurosensory processing, including nociceptive transduction. Thus, ATP signaling may participate in dentin hypersensitivity and dental pain. In this study, we investigated whether pannexins, which can form mechanosensitive ATP-permeable channels, are present in human dental pulp. We also assessed the existence and functional activity of ecto-ATPase for extracellular ATP degradation. We further tested if ATP is released from dental pulp upon dentin mechanical or thermal stimulation that induces dentin hypersensitivity and dental pain and if pannexin or pannexin/gap junction channel blockers reduce stimulation-dependent ATP release. Using immunofluorescence staining, we demonstrated immunoreactivity of pannexin 1 and 2 in odontoblasts and their processes extending into the dentin tubules. Using enzymatic histochemistry staining, we also demonstrated functional ecto-ATPase activity within the odontoblast layer, subodontoblast layer, dental pulp nerve bundles, and blood vessels. Using an ATP bioluminescence assay, we found that mechanical or cold stimulation to the exposed dentin induced ATP release in an in vitro human tooth perfusion model. We further demonstrated that blocking pannexin/gap junction channels with probenecid or carbenoxolone significantly reduced external dentin stimulation-induced ATP release. Our results provide evidence for the existence of functional machinery required for ATP release and degradation in human dental pulp and that pannexin channels are involved in external dentin stimulation-induced ATP release. These findings support a plausible role for ATP signaling in dentin hypersensitivity and dental pain.

Expression of ecto-ATPase NTPDase2 in human dental pulp.

Dental pulpal nerve fibers express ionotropic adenosine triphosphate (ATP) receptors, suggesting that ATP signaling participates in the process of dental nociception. In this study, we investigated if the principal enzymes responsible for extracellular ATP hydrolysis, namely, nucleoside triphosphate diphosphohydrolases (NTPDases), are present in human dental pulp. Immunohistochemical and immunofluorescence experiments showed that NTPDase2 was predominantly expressed in pulpal nerve bundles, Raschkow's nerve plexus, and in the odontoblast layer. NTPDase2 was expressed in pulpal Schwann cells, with processes accompanying the nerve fibers and projecting into the odontoblast layer. Odontoblasts expressed the gap junction protein, connexin43, which can form transmembrane hemichannels for ATP release. NTPDase2 was localized close to connexin43 within the odontoblast layer. These findings provide evidence for the existence of an apparatus for ATP release and degradation in human dental pulp, consistent with the involvement of ATP signaling in the process of dentin sensitivity and dental pain.

COX 2 selectivity of non-steroidal anti-inflammatory drugs and perioperative blood loss in hip surgery. A randomized comparison of indomethacin and meloxicam.

BACKGROUND: In this prospective randomized study we tested the hypothesis that use of more cyclo-oxygenase 2 (COX 2)-selective non-steroidal anti-inflammatory drugs (NSAIDs) can reduce perioperative blood loss compared with non-selective NSAIDs. METHODS: Data from 200 patients who underwent total hip replacement were studied. Two NSAIDs were compared: indomethacin 50 mg (n = 82) and meloxicam 15 mg (n = 86). Both NSAIDs were given orally 1 h before surgery. RESULTS: The two groups were not different with respect to age, gender, ASA class or duration of surgery. When indomethacin was used preoperatively, intraoperative blood loss was 623 +/- 243 mL (mean +/- SD) and postoperative blood loss 410 +/- 340 mL. After meloxicam, these values were 524 +/- 304 mL and 358 +/- 272 mL, respectively. Total perioperative blood loss after meloxicam was 17% (P < 0.05) less than that observed after indomethacin. CONCLUSION: Perioperative blood loss after meloxicam is less than after indomethacin. These in vivo findings are consistent with in vitro results using selective COX 2 NSAIDs.

Does ibuprofen increase perioperative blood loss during hip arthroplasty?

BACKGROUND AND OBJECTIVE: To determine whether prior exposure of non-steroidal anti-inflammatory drugs increases perioperative blood loss associated with major orthopaedic surgery. METHODS: Fifty patients scheduled for total hip replacement were allocated to two groups (double blind, randomized manner). All patients were pretreated for 2 weeks before surgery: Group 1 with placebo drug, Group 2 with ibuprofen. All patients were injected intrathecally with bupivacaine 20mg plus morphine 0.1 mg, in a total volume of 4 mL, to provide surgical anaesthesia. RESULTS: The presence of severe adverse effects caused eight patients in the ibuprofen group and six in the placebo group to terminate their participation in the trial. The perioperative blood loss increased by 45% in the ibuprofen group compared with placebo. The total (+/-SD) blood loss in the ibuprofen group was 1161 (+/-472) mL versus 796 (+/-337) mL in the placebo group. CONCLUSIONS: Pretreatment with ibuprofen before elective total hip surgery increases the perioperative blood loss significantly. Early discontinuation of non-selective non-steroidal anti-inflammatory drugs is advised.

Predictive performance of a physiological model for enflurane closed-circuit anaesthesia: effects of continuous cardiac output measurements and age-related solubility data.

BACKGROUND: The disposition of inhalation anaesthetics is governed by the factors described in the Fick principle. METHODS: We have recalibrated a previously validated physiological model for enflurane closed-circuit inhalation anaesthesia, using individual continuous cardiac output measurements as well as age-related enflurane solubility coefficients as inputs to the model. Two model versions using 'calculated' (Brody's formula) or 'measured' (thoracic electrical bioimpedance) cardiac output values, and two versions with 'standard' (fixed) or 'age-related' solubility coefficients were formulated. RESULTS: Data from 62 ophthalmic surgical patients were used to validate the predictive performance of the four model versions. The root mean squared errors (total error) and scatters (error variation) were similar with the extended model versions, but the group biases (systematic error component) were significantly less with the model versions that included age-related solubility compared with the versions using standard solubility coefficients (bias -0.76/-0.78% vs -3.44/-3.60%). CONCLUSION: The inclusion of age-related solubility coefficients but not of continuous cardiac output measurements improves the predictive performance of the physiological model for closed-circuit inhalation anaesthetic conditions in routine clinical practice.

Functional effects of central core disease mutations in the cytoplasmic region of the skeletal muscle ryanodine receptor.

Central core disease (CCD) is a human myopathy that involves a dysregulation in muscle Ca(2)+ homeostasis caused by mutations in the gene encoding the skeletal muscle ryanodine receptor (RyR1), the protein that comprises the calcium release channel of the SR. Although genetic studies have clearly demonstrated linkage between mutations in RyR1 and CCD, the impact of these mutations on release channel function and excitation-contraction coupling in skeletal muscle is unknown. Toward this goal, we have engineered the different CCD mutations found in the NH(2)-terminal region of RyR1 into a rabbit RyR1 cDNA (R164C, I404M, Y523S, R2163H, and R2435H) and characterized the functional effects of these mutations after expression in myotubes derived from RyR1-knockout (dyspedic) mice. Resting Ca(2)+ levels were elevated in dyspedic myotubes expressing four of these mutants (Y523S > R2163H > R2435H R164C > I404M RyR1). A similar rank order was also found for the degree of SR Ca(2)+ depletion assessed using maximal concentrations of caffeine (10 mM) or cyclopiazonic acid (CPA, 30 microM). Although all of the CCD mutants fully restored L-current density, voltage-gated SR Ca(2)+ release was smaller and activated at more negative potentials for myotubes expressing the NH(2)-terminal CCD mutations. The shift in the voltage dependence of SR Ca(2)+ release correlated strongly with changes in resting Ca(2)+, SR Ca(2)+ store depletion, and peak voltage-gated release, indicating that increased release channel activity at negative membrane potentials promotes SR Ca(2)+ leak. Coexpression of wild-type and Y523S RyR1 proteins in dyspedic myotubes resulted in release channels that exhibited an intermediate degree of SR Ca(2)+ leak. These results demonstrate that the NH(2)-terminal CCD mutants enhance release channel sensitivity to activation by voltage in a manner that leads to increased SR Ca(2)+ leak, store depletion, and a reduction in voltage-gated Ca(2)+ release. Two fundamentally distinct cellular mechanisms (leaky channels and EC uncoupling) are proposed to explain how altered release channel function caused by different mutations in RyR1 could result in muscle weakness in CCD.

Ca2+ release through ryanodine receptors regulates skeletal muscle L-type Ca2+ channel expression.

Skeletal muscle obtained from mice that lack the type 1 ryanodine receptor (RyR-1), termed dyspedic mice, exhibit a 2-fold reduction in the number of dihydropyridine binding sites (DHPRs) compared with skeletal muscle obtained from wild-type mice (Buck, E. D., Nguyen, H. T., Pessah, I. N., and Allen, P. D. (1997) J. Biol. Chem. 272, 7360-7367 and Fleig, A., Takeshima, H., and Penner, R. (1996) J. Physiol. (Lond.) 496, 339-345). To probe the role of RyR-1 in influencing L-type Ca(2+) channel (L-channel) expression, we have monitored functional L-channel expression in the sarcolemma using the whole-cell patch clamp technique in normal, dyspedic, and RyR-1-expressing dyspedic myotubes. Our results indicate that dyspedic myotubes exhibit a 45% reduction in maximum immobilization-resistant charge movement (Q(max)) and a 90% reduction in peak Ca(2+) current density. Calcium current density was significantly increased in dyspedic myotubes 3 days after injection of cDNA encoding either wild-type RyR-1 or E4032A, a mutant RyR-1 that is unable to restore robust voltage-activated release of Ca(2+) from the sarcoplasmic reticulum (SR) following expression in dyspedic myotubes (O'Brien, J. J., Allen, P. D., Beam, K., and Chen, S. R. W. (1999) Biophys. J. 76, A302 (abstr.)). The increase in L-current density 3 days after expression of either RyR-1 or E4032A occurred in the absence of a change in Q(max). However, Q(max) was increased 85% 6 days after injection of dyspedic myotubes with cDNA encoding the wild-type RyR-1 but not E4032A. Because normal and dyspedic myotubes exhibited a similar density of T-type Ca(2+) current (T-current), the presence of RyR-1 does not appear to cause a general overall increase in protein synthesis. Thus, long-term expression of L-channels in skeletal myotubes is promoted by Ca(2+) released through RyRs occurring either spontaneously or during excitation-contraction coupling.

Excitation--contraction uncoupling by a human central core disease mutation in the ryanodine receptor.

Central core disease (CCD) is a human congenital myopathy characterized by fetal hypotonia and proximal muscle weakness that is linked to mutations in the gene encoding the type-1 ryanodine receptor (RyR1). CCD is thought to arise from Ca(2+)-induced damage stemming from mutant RyR1 proteins forming "leaky" sarcoplasmic reticulum (SR) Ca(2+) release channels. A novel mutation in the C-terminal region of RyR1 (I4898T) accounts for an unusually severe and highly penetrant form of CCD in humans [Lynch, P. J., Tong, J., Lehane, M., Mallet, A., Giblin, L., Heffron, J. J., Vaughan, P., Zafra, G., MacLennan, D. H. & McCarthy, T. V. (1999) Proc. Natl. Acad. Sci. USA 96, 4164--4169]. We expressed in skeletal myotubes derived from RyR1-knockout (dyspedic) mice the analogous mutation engineered into a rabbit RyR1 cDNA (I4897T). Here we show that homozygous expression of I4897T in dyspedic myotubes results in a complete uncoupling of sarcolemmal excitation from voltage-gated SR Ca(2+) release without significantly altering resting cytosolic Ca(2+) levels, SR Ca(2+) content, or RyR1-mediated enhancement of dihydropyridine receptor (DHPR) channel activity. Coexpression of both I4897T and wild-type RyR1 resulted in a 60% reduction in voltage-gated SR Ca(2+) release, again without altering resting cytosolic Ca(2+) levels, SR Ca(2+) content, or DHPR channel activity. These findings indicate that muscle weakness suffered by individuals possessing the I4898T mutation involves a functional uncoupling of sarcolemmal excitation from SR Ca(2+) release, rather than the expression of overactive or leaky SR Ca(2+) release channels.

Prolonged depolarization promotes fast gating kinetics of L-type Ca2+ channels in mouse skeletal myotubes.

The effects of prolonged conditioning depolarizations on the activation kinetics of skeletal L-type calcium currents (L-currents) were characterized in mouse myotubes using the whole-cell patch clamp technique. The sum of two exponentials was required to adequately fit L-current activation and enabled determination of both the amplitudes (A(fast) and A(slow)) and time constants (tau(fast) and tau(slow)) of each component comprising the macroscopic current. Prepulses sufficient to activate (200 ms) or inactivate (10 s) L-channels did not alter tau(fast), tau(slow), or the fractional contribution of either the fast (A(fast)/(A(fast) + A(slow)) or slow (A(slow)/(A(fast) + A(slow))) amplitudes of subsequently activated L-currents. Prolonged depolarizations (60 s to +40 mV) resulted in the conversion of skeletal L-current to a fast gating mode following brief repriming intervals (3-10 s at -80 mV). Longer repriming intervals (30-60 s at -80 mV) restored L-channels to a predominantly slow gating mode. Accelerated L-currents originated from L-type calcium channels since they were completely blocked by a dihydropyridine antagonist (3 microM nifedipine) and exhibited a voltage dependence of activation similar to that observed in the absence of conditioning prepulses. The degree of L-current acceleration produced following prolonged depolarization was voltage dependent. For test potentials between +10 and +50 mV, the fractional contribution of Afast to the total current decreased exponentially with the test voltage (e-fold approximately 38 mV). Thus, L-current acceleration was most significant at more negative test potentials (e.g. +10 mV). Prolonged depolarization also accelerated L-currents recorded from myotubes derived from RyR1-knockout (dyspedic) mice. These results indicate that L-channel acceleration occurs even in the absence of RyR1, and is therefore likely to represent an intrinsic property of skeletal L-channels. The results describe a novel experimental protocol used to demonstrate that slowly activating mammalian skeletal muscle L-channels are capable of undergoing rapid, voltage-dependent transitions during channel activation. The transitions underlying rapid L-channel activation may reflect rapid transitions of the voltage sensor used to trigger the release of calcium from the sarcoplasmic reticulum during excitation-contraction coupling.

Itching after intrathecal morphine. Incidence and treatment.

This study was designed to determine whether low doses of intrathecal morphine still result in itching and it evaluates the outcome of a standardized treatment using promethazine and - for intractable itch - naloxone. Patients (n = 143) scheduled for total hip surgery were allocated to four groups (in a double blind manner) with bupivacaine 20 mg in 4 mL but different doses of intrathecal morphine: Group I, 0.025 mg, Group II, 0.05 mg, Group III, 0.1 mg and Group IV, 0.2 mg. The presence or absence of itching was noted every three hours for a 24-h period. When required, standardized treatment was provided. The incidence of itching was: Group I: 14. 3%; Group II: 21.6%; Group III: 48.6%; and, Group IV: 61.7%. Itch was treated by administering promethazine intramuscularly in 2.9% (Group I); 8.1% (Group II); 10.8% (Group III), and 8.9% (Group IV), respectively. Only in group IV there was a single patient who needed naloxone to treat itching. The incidence and severity of itching is a dose-related side-effect in the dose range of 0.025-0.2 mg of intrathecal morphine. Itching still occurs after the low doses of intrathecal morphine, but symptoms vanish after promethazine 25 mg intramuscularly.

The incidence of transient neurological symptoms after spinal anaesthesia with lidocaine compared to prilocaine.

The purpose of this double-blind study was to investigate the incidence of transient neurological symptoms after the use of isobaric lidocaine and isobaric prilocaine for spinal anaesthesia. Seventy patients (ASA 1-2, age between 18 and 70 years) were randomly assigned to two groups of 35 patients each, to receive either isobaric 2% lidocaine 4 ml or isobaric 2% prilocaine 4 ml intrathecally, at the L3-4 interspace. One patient in the prilocaine group could not be included because data were incomplete. On the first postoperative day, patients were evaluated for transient neurological symptoms. Pain was scored on a 10-point scale. Seven patients (20%) in the lidocaine group had transient neurological symptoms with a mean pain score of 5.3, whereas no patient in the prilocaine group had these complaints (p = 0.006). Symptoms disappeared within 4 days. Prilocaine results in a lower incidence of transient neurological symptoms than lidocaine intrathecally and therefore it is more suitable for short surgical procedures.

Substance P.

Substance P is considered to be an important neuropeptide in nociceptive processes. Although substance P was described more than 60 years ago, there is still controversy about its exact role in nociception. This article reviews the current knowledge about the function of substance P in pain. Special emphasis is put on how to use this knowledge in the development of new ways to treat pain.

Early assessment of skeletal muscle damage after ischaemia-reperfusion injury using Tc-99m-glucarate.

PURPOSE: After acute arterial obstruction of the lower extremity, muscle damage is the critical determinant for clinical outcome. The extent of muscle damage and limb viability are currently assessed by clinical examination, which is inaccurate. Tc-99m-pyrophosphate (PYP) has been applied for imaging ischaemia-reperfusion damage. More recently, a new imaging agent, Tc-99m-glucarate (GLUC), was introduced for delineating early myocardial infarction after ischaemia-reperfusion. The aim of this study was to determine if GLUC could delineate early skeletal muscle damage after ischaemia-reperfusion. Both tracers were used in a novel murine model of hindlimb ischaemia-reperfusion. METHODS: In anaesthetised mice, ischaemia of one hindlimb was maintained for 2, 3 and 4h using a tourniquet, followed by a reperfusion period of 1h. Additionally, reperfusion periods of 3, 24 and 96h were studied after 3h of ischaemia. PYP or GLUC was injected 45min before end of reperfusion. Concentrations of both agents were determined in blood, reperfused and contralateral muscle. Reperfused-to-contralateral muscle ratios were calculated. In separate experiments, muscle biopsies were obtained for histologic examination. RESULTS: Ischaemia and reperfusion damage was demonstrated histologically. Using scintigraphy GLUC depicted reperfusion significantly better than PYP. After 2, 3 and 4h of ischaemia, the reperfused-to-contralateral ratios for GLUC were 10.7+/-0.9, 8.9+/-0.9 and 8.6+/-1.1, as compared to 4.5+/-0.7, 4.9+/-0.4 and 4.5+/-0.4 for PYP (P<0.05 at all points). For longer periods of reperfusion, the ratios for GLUC decreased to similar levels as observed for PYP. CONCLUSION: The present study indicates that GLUC is a specific early marker of myocyte necrosis after ischaemia-reperfusion. GLUC may become an useful agent for clinical, early, non-invasive monitoring of skeletal muscle damage after ischaemia-reperfusion.

Low serum promotes maturation of excitation-contraction coupling in myotubes.

Patch-clamping and the simultaneous fluorescence measurement of cytoplasmic Ca2+ ([Ca2+]i) were used to analyze the effect of serum on the functional features of excitation-contraction (E-C) coupling in mouse skeletal myotubes. In high-serum-treated (10%) myotubes, depolarization elicited Ca2+ release which continued for tens of milliseconds following the end of the pulse, after which [Ca2+]i decayed slowly. In low-serum-treated (0.5%) myotubes, the Ca2+ transient caused by depolarization had an increased rate of rise and peak amplitude, and [Ca2+]i began to decay rapidly upon repolarization. When a depolarizing pulse (0.5-1.0 s) was applied to low-serum-treated myotubes during a Ca2+ transient induced by 5-10 mM caffeine, repolarization usually caused the caffeine transient to terminate rapidly (RISC; repolarization-induced stop of caffeine-induced Ca2+ release). The RISC was less prominent in high-serum-treated myotubes. These results suggest that low serum promotes the maturation of myotubes so that Ca(2+)-release and Ca(2+)-removal activities are accelerated. Additionally, the essential features of the communication between the voltage sensor and the Ca(2+)-release channel are shared by myotubes and adult muscle fibers.

Correlation dimension of the human electroencephalogram corresponds with cognitive load.

This study aimed at assessing the effects of cognitive activity and mental task load on the correlation dimension of the human electroencephalogram (EEG). Three experimental conditions were created: a baseline condition and two cognitive task conditions, a calculation task and a time estimation task. The calculation task was supposed to induce a higher mental load than the time estimation task, which is regarded as a less complex one. This was verified by a subjective rating scale. All conditions differed significantly in subjective estimated task load. The correlation dimension appeared to be higher in both task conditions compared to the baseline condition. A comparison of the two tasks indicated that the difference in correlation dimension between calculation and time estimation was also significant, with the highest value for calculation. It is concluded that cognitive and mental activity is associated with a higher correlation dimension in the EEG. This implies that the correlation dimension is a sensitive parameter in the analysis of electrical brain activity.