The mandibular muscle receptor organ of Homarus gammarus (L.) (crustacea,decapoda)

Summary A muscle receptor organ is present in the mandible of macruran decapods. The mandibular muscle receptor organ (Mand. MRO) of Homarus gammarus (L.) consists of a ribbon of muscle innervated at its ventral insertion by 10–20 multiterminal sensory neurones. The sensory cells have a small number of dendritic processes.The receptor muscle exhibits some structural properties of both fast and slow muscle. The mean sarcomere length is similar to that of the slow abdominal MRO but the receptor muscle in cross section has a punctate distribution of myofibril bundles more typical of fast muscle.This work was supported by Science Research Council grants B/SR/1871 and BR/G/585.     

A piece-wise non-linear elastic stress expression of human and pig coronary arteries tested in vitro.

Eight human and nineteen pig unembalmed proximal left anterior descending and circumflex coronary arteries were subjected to linear volume changes (2 s ramp time) at three fixed axial extensions while immersed in a physiological saline bath at body temperature. Measured parameters included: lumen pressure, outside diameter, axial force, and axial extension. The deformations were measured using a video dimensional analyzer. The arteries were inflated to pressures well above the physiological range at each axial extension. A latex inner tube was placed inside of each specimen to prevent leakage, and its effects upon the measured stresses were corrected analytically. With this method, the average circumferential and axial stresses could be computed directly from the experimental data. In both directions the average stresses measured displayed two distinct regions: stresses occurring for small diameter changes (physiological pressures) and stresses occurring for large diameter changes (high pressures). The resulting average small strain and large strain stress components were curve-fit separately and, when reassembled, provided a piece-wise model of the stress response of coronary arteries over a wide range of inflation pressures and axial extensions.     

Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart. Role of Ca2+/calmodulin-dependent protein kinase II

Returning to normal pH after acidosis, similar to reperfusion after ischemia, is prone to arrhythmias. The type and mechanisms of these arrhythmias have never been explored and were the aim of the present work. Langendorff-perfused rat/mice hearts and rat-isolated myocytes were subjected to respiratory acidosis and then returned to normal pH. Monophasic action potentials and left ventricular developed pressure were recorded. The removal of acidosis provoked ectopic beats that were blunted by 1 muM of the CaMKII inhibitor KN-93, 1 muM thapsigargin, to inhibit sarcoplasmic reticulum (SR) Ca(2+) uptake, and 30 nM ryanodine or 45 muM dantrolene, to inhibit SR Ca(2+) release and were not observed in a transgenic mouse model with inhibition of CaMKII targeted to the SR. Acidosis increased the phosphorylation of Thr(17) site of phospholamban (PT-PLN) and SR Ca(2+) load. Both effects were precluded by KN-93. The return to normal pH was associated with an increase in SR Ca(2+) leak, when compared with that of control or with acidosis at the same SR Ca(2+) content. Ca(2+) leak occurred without changes in the phosphorylation of ryanodine receptors type 2 (RyR2) and was blunted by KN-93. Experiments in planar lipid bilayers confirmed the reversible inhibitory effect of acidosis on RyR2. Ectopic activity was triggered by membrane depolarizations (delayed afterdepolarizations), primarily occurring in epicardium and were prevented by KN-93. The results reveal that arrhythmias after acidosis are dependent on CaMKII activation and are associated with an increase in SR Ca(2+) load, which appears to be mainly due to the increase in PT-PLN.     

The role of internal pressure and muscle activation during locust oviposition

The oviposition of female locusts is a complex behaviour that includes a dramatic extension of the abdomen. The role of internal pressure during oviposition was investigated by monitoring the intra-tracheal pressure and the activity of selected longitudinal muscles, while movements of the abdomen were visualised with a video imaging system. Locust oviposition consists of a sequence of four distinct phases: (i) probing the substrate and digging without elongation of the abdomen, (ii) longitudinal extension of the abdomen up to four times its normal length, (iii) laying packages of eggs while (iv) gradually withdrawing the abdomen. During extension, neurograms and myograms of selected longitudinal muscles revealed a decreased level of activity. When the abdomen retracted to its normal length, muscle activity re-appeared. In phases two and three, rising internal pressure prevented the abdomen from slipping back when the valves released their lateral grip from the substrate. Locking the genital segments in the hole by relative bending kept the abdomen in place when producing foam or laying eggs. Intra-abdominal pressure, therefore, is not the main cause of abdominal extension, but rather maintains extension when no mechanical locking in the hole prevents the abdomen from elastic retraction.     

Background ventilatory stimulus as a determinant of load compensation

Compensation for inspiratory flow-resistive loading was compared during progressive hypercapnia and incremental exercise to determine the effect of changing the background ventilatory stimulus and to assess the influence of the interindividual variability of the unloaded CO2 response on evaluation of load compensation in normal subjects. During progressive hypercapnia, ventilatory response was incompletely defended with loading (mean unloaded delta VE/delta PCO2 = 3.02 +/- 2.29, loaded = 1.60 +/- 0.67 1.min-1.Torr-1 CO2, where VE is minute ventilation and PCO2 is CO2 partial pressure; P less than 0.01). Furthermore the degree of defense of ventilation with loading was inversely correlated with the magnitude of the unloaded CO2 response. During exercise, loading produced no depression in ventilatory response (mean delta VE/delta VCO2 unloaded = 20.5 +/- 1.9, loaded = 19.2 +/- 2.5 l.min-1.l-1.min-1 CO2 where VCO is CO2 production; P = NS), and no relationship was demonstrated between degree of defense of the exercise ventilatory response and the unloaded CO2 response. Differences in load compensation during CO2 rebreathing and exercise suggest the presence of independent ventilatory control mechanisms in these states. The type of background ventilatory stimulus should therefore be considered in load compensation assessment.     

Contribution of the 3'- to 5'-exonuclease activity of herpes simplex virus type 1 DNA polymerase to the fidelity of DNA synthesis

Nucleotide incorporation by the herpes simplex virus type 1 DNA polymerase catalytic subunit (pol) is less faithful than for most replicative DNA polymerases, despite the presence of an associated 3'- to 5'-exonuclease (exo) activity. To determine the aspects of fidelity affected by the exo activity, nucleotide incorporation and mismatch extension frequency for purified wild-type and an exo-deficient mutant (D368A) pol were compared using primer/templates that varied at only a single position. For both enzymes, nucleotide discrimination during incorporation occurred predominantly at the level of K(m) for nucleotide and was the major contributor to fidelity. The contribution of the exo activity to reducing the efficiency of formation of half of all possible mispairs was 6-fold or less, and 30-fold when averaged for the formation of all possible mispairs. In steady-state reactions, mismatches imposed a significant kinetic barrier to extension independent of exo activity. However, during processive DNA synthesis in the presence of only three nucleotides, misincorporation and mismatch extension were efficient for both exo-deficient and wild-type pol catalytic subunits, although slower kinetics of mismatch extension by the exo-deficient pol were observed. The UL42 processivity factor decreased the extent of misincorporation by both the wild-type and the exo-deficient pol to similar levels, but mismatch extension by the wild-type pol.UL42 complex was much less efficient than by the mutant pol.UL42. Thus, despite relatively frequent (1 in 300) misincorporation events catalyzed by wild-type herpes simplex virus pol.UL42 holoenzyme, mismatch extension occurs only rarely, prevented in part by the kinetic barrier to extending a mismatch. The kinetic barrier also increases the probability that a mismatched primer terminus will be transferred to the exo site where it can be excised by the associated exo activity and subsequently extended with correct nucleotide.     

Electromyographic comparison of standard and modified closed-chain isometric knee extension exercises

The purpose of this study was to compare electromyographic (EMG) activity during open kinetic chain (OKC) and a modified closed kinetic chain (MCKC) knee extension exercises. Both OKC and closed kinetic chain (CKC) exercises provide benefits when devising conditioning programs; however, there are no exercises that combine the benefits of both exercises. Subjects performed maximum isometric knee extensions for both traditional OKC and MCKC knee extension exercises. Surface electrodes were placed on 8 lower-extremity muscles. One second of integrated EMG activity followed 95% maximal knee extension force. The following muscles demonstrated greater EMG activity during the MCKC vs. the OKC knee extension exercises: vastus medialis, medial hamstring, lateral hamstrings, and gluteus maximus. There was no difference between force output between the 2 conditions. This study demonstrates that modifications to traditional OKC exercises demonstrate some characteristics of CKC exercises, and therefore provide another avenue of rehabilitation or strengthening.     

Oxidative damage to Ca2+-ATPase sarcoplasmic reticulum by HOCl and protective effect of some antioxidants

Injury of rabbit skeletal sarcoplasmic reticulum (SR) induced by hypochlorous acid (HOCl) was studied. HOCl inhibited Ca2+-ATPase activity in a concentration-dependent manner (IC50=100 micromol/l). The concentration of 13.5 micromol/l HOCl reduced the level of sulfhydryl (SH) groups by 50%, yet it did not influence the enzyme activity. In comparison with SH group oxidation and enzyme activity inhibition, a significantly longer time was necessary for the generation of protein carbonyls in SR injured by HOCl. Protective effects of some antioxidants (stobadine, trolox, EGb 761, Pycnogenol) were studied in SR oxidatively injured by HOCl. Trolox and EGb 761 exerted a protective effect on ATPase activity and on SH groups of SR oxidatively modified by HOCl. Stobadine and Pycnogenol inhibited markedly protein carbonyl formation. Stobadine was the only antioxidant able to scavenge HOCl. In conclusion, the protective effects of antioxidants against decrease of Ca2+-ATPase activity induced by HOCl might be caused by protection of SH groups. The compounds with both antioxidant and Ca2+-ATPase protecting effect offer dual defense against tissue damage occurring, e.g. in aging process.     

The activity of abdominal stretch receptors during non-giant swimming in the crayfish<Emphasis Type="Italic"> Cherax destructor</Emphasis> and their role in hydrodynamic efficiency

Recordings were made from the nerve innervating the stretch receptors of the abdominal muscle receptor organs and slow extensor muscles of tethered crayfish, Cherax destructor, during so-called non-giant swimming. The stretch receptors were active during the flexor phase of swimming but the duration and pattern of activity varied from cycle to cycle. Their pattern of firing was modified by the activity of the large accessory neurons which make direct inhibitory synapses upon them. Neither the stretch receptors nor the accessory neurons were active during the extensor phase of the cycle. The timing and extent of tailfan movements during the period of stretch receptor activity were measured from video records before and after the stretch receptor nerves were cut in the second to fifth segments. The promotion of the tailfan during flexion was significantly delayed and the minimum angle to which the uropods were remoted at the end of flexion significantly larger in denervated animals. We propose that afferent information from the stretch receptors coordinates the timing and extent of tailfan movements according to variations in the positioning and movement of the abdominal segments such that the hydrodynamic efficiency of the tailfan is enhanced on a cycle by cycle basis during non-giant swimming.Abbreviations A# abdominal segment number - Acc accessory neuron - LUU large unidentified unit - MRO muscle receptor organ - NGS non-giant swimming - SEMN slow extensor motor neuron - SR stretch receptor neuron     

Respiratory muscle responses elicited by dorsal periaqueductal gray stimulation in rats

The periaqueductal gray matter is an essential neural substrate for central integration of defense behavior and accompanied autonomic responses. The dorsal half of the periaqueductal gray matter (dPAG) is also involved in mediating emotional responses of anxiety and fear, psychological states that often are associated with changes in ventilation. However, information regarding respiratory modulation elicited from this structure is limited. The present study was undertaken to investigate the relationship between stimulus frequency and magnitude on ventilatory pattern and respiratory muscle activity in urethane-anesthetized, spontaneously breathing rats. Electrical stimulation in the dPAG-recruited abdominal muscle activity increased ventilation and increased respiratory frequency by significantly shortening both inspiratory time and expiratory time. Ventilation increased within the first breath after the onset of stimulation, and the respiratory response increased with increasing stimulus frequency and magnitude. dPAG stimulation also increased baseline EMG activity in the diaphragm and recruited baseline external abdominal oblique EMG activity, normally quiescent during eupneic breathing. Significant changes in cardiorespiratory function were only evoked by stimulus intensities >10 microA and when stimulus frequencies were >10 Hz. Respiratory activity of both the diaphragm and abdominal muscles remained elevated for a minimum of 60 s after cessation of stimulation. These results demonstrate that there is a short-latency respiratory response elicited from the dPAG stimulation, which includes both inspiratory and expiratory muscles. The changes in respiratory timing suggest rapid onset and sustained poststimulus dPAG modulation of the brain stem respiratory network that includes expiratory muscle recruitment.     

Activation of cardiac ryanodine receptors by cardiac glycosides

This study investigated the effects of cardiac glycosides on single-channel activity of the cardiac sarcoplasmic reticulum (SR) Ca2+ release channels or ryanodine receptor (RyR2) channels and how this action might contribute to their inotropic and/or toxic actions. Heavy SR vesicles isolated from canine left ventricle were fused with artificial planar lipid bilayers to measure single RyR2 channel activity. Digoxin and actodigin increased single-channel activity at low concentrations normally associated with therapeutic plasma levels, yielding a 50% of maximal effect of approximately 0.2 nM for each agent. Channel activation by glycosides did not require MgATP and occurred only when digoxin was applied to the cytoplasmic side of the channel. Similar results were obtained in human RyR2 channels; however, neither the crude skeletal nor the purified cardiac channel was activated by glycosides. Channel activation was dependent on [Ca2+] on the luminal side of the bilayer with maximal stimulation occurring between 0.3 and 10 mM. Rat RyR2 channels were activated by digoxin only at 1 microM, consistent with the lower sensitivity to glycosides in rat heart. These results suggest a model in which RyR2 channel activation by digoxin occurs only when luminal [Ca2+] was increased above 300 microM (in the physiological range). Consequently, increasing SR load (by Na+ pump inhibition) serves to amplify SR release by promoting direct RyR2 channel activation via a luminal Ca2+-sensitive mechanism. This high-affinity effect of glycosides could contribute to increased SR Ca2+ release and might play a role in the inotropic and/or toxic actions of glycosides in vivo.     

Tactile stimulation of the swimmeret alters motor programs for abdominal posture in the lobsterHomarus americanus

The influence of mechanosensory stimulation of a second segment swimmeret upon the abdominal postural program was examined in an isolated abdominal nerve cord-swimmeret preparation. The swimmeret was stimulated in several different ways to assess the extent of influence exerted on abdominal positioning. Localized tactile stimulation of the swimmeret surface with a mechanical probe usually generated flexion inhibition where the flexor inhibitor (f5) was activated while the small and medium flexor excitors were inhibited. Flexion inhibition was much stronger in females than males. In 50% of the animals a weak flexion excitation was seen. After 3-6 hours the response of one-third of these preparations changed to flexion inhibition. Strong manual stimulation of the swimmeret surface inhibited all of the flexor excitors (f1, f2, f3, f4, and f6) while exciting the inhibitor f5 and increasing extensor activity. Similar extension responses were observed in both sexes. Repeated tactile stimulation of the swimmeret surface elicited a response similar to that evoked during manual stimulation. The strongest extension response was produced at 2 Hz which falls within the normal range of swimmeret beating in intact lobsters. Similar extension responses were also obtained during spontaneous swimmeret beating and rhythmic manual movement of the swimmeret.(ABSTRACT TRUNCATED AT 250 WORDS)     

Load compensation and respiratory muscle function during sleep.

The sleeping state places unique demands on the ventilatory control system. The sleep-induced increase in airway resistance, the loss of consciousness, and the need to maintain the sleeping state without frequent arousals require the presence of complex compensatory mechanisms. The increase in upper airway resistance during sleep represents the major effect of sleep on ventilatory control. This occurs because of a loss of muscle activity, which narrows the airway and also makes it more susceptible to collapse in response to the intraluminal pressure generated by other inspiratory muscles. The magnitude and timing of the drive to upper airway vs. other inspiratory pump muscles determine the level of resistance and can lead to inspiratory flow limitation and complete upper airway occlusion. The fall in ventilation with this mechanical load is not prevented, as it is in the awake state, because of the absence of immediate compensatory responses during sleep. However, during sleep, compensatory mechanisms are activated that tend to return ventilation toward control levels if the load is maintained. Upper airway protective reflexes, intrinsic properties of the chest wall, muscle length-compensating reflexes, and most importantly chemoresponsiveness of both upper airway and inspiratory pump muscles are all present during sleep to minimize the adverse effect of loading on ventilation. In non-rapid-eye-movement sleep, the high mechanical impedance combined with incomplete load compensation causes an increase in arterial PCO2 and augmented respiratory muscle activity. Phasic rapid-eye-movement sleep, however, interferes further with effective load compensation, primarily by its selective inhibitory effects on the phasic activation of postural muscles of the chest wall. The level and pattern of ventilation during sleep in health and disease states represent a compromise toward the ideal goal, which is to achieve maximum load compensation and meet the demand for chemical homeostasis while maintaining sleep state.     

Sperm duct contractions mediate centrally evoked sperm release in goldfish

In order to determine the peripheral mechanisms underlying sperm release (SR) in goldfish, the contractile activity of the sperm ducts (SD) and testes were monitored during SR responses evoked by electrical stimulation of the brain. Electrical stimulation of the brain triggered testicular and SD contractions, and SR, while electrical stimulation of the genital nerve branch to the SD evoked only SD contractions and SR. Centrally activated SD contractions and SR were blocked by sectioning the SD genital nerve, while testicular contractions were unaffected. Testicular contractions do not appear necessary for centrally evoked SR since the response can be elicited from preparations in which the testes were separated from the SD. The results indicate that SR in goldfish is primarily mediated by the SD and not the testes. Testicular contractions may, however, serve to load the SD with milt. The functional significance of the central pathway(s) associated with SD and testicular contractions are discussed.     

A Phylogeny‐Based Comparison of Tarantula Spider Anti‐Predator Behavior Reveals Correlation of Morphology and Behavior

We studied anti‐predator strategies in nine species of tarantulas from Asia, Africa, and the Americas. Tarantulas in the New World possess urticating hairs which induce inflammation when in contact with vertebrate mucus membranes and skin. In contrast, tarantulas from the Old World lack this defense but are observed to exhibit a much greater willingness to escalate to an active defense when provoked. We had three goals: (1) describe the behaviors exhibited by each taxon in response to two levels of provocation, (2) look for the presence of alternative classes of anti‐predator strategy as predicted by the Old World–New World dichotomy in aggressive defense, and (3) examine the evolution of these behaviors in the context of the phylogeny of the group. We compared the response of nine different mygalomorph spider genera to two levels of aversive stimuli: puffs of air and prodding. We found that the overall structure of the defensive behavior was similar between the different taxa, consisting of fleeing, rearing, striking, and biting. Some genera did exhibit unique behaviors such as stridulating (Hysterocrates) or rocking (Haplopelma and Selenocosmia). We found that the genera from the New World exhibited low levels of escalation in their defense behaviors, while those from the Old World readily escalated to striking and biting. Our findings are consistent with the hypothesis that the possession of urticating hairs is associated with very low levels of active defense behaviors such as striking and biting. The phylogenetic analysis indicates that both the notable levels of aggression displayed by the African taxa tested and the relative passivity of the New World tarantulas each represents a synapomorphy.     

Hopping and swimming in the leopard frog Rana pipiens: II. A comparison of muscle activities

Electromyography (EMG) was used to examine muscle activity of the major hip, knee, and ankle extensors during both hopping and swimming in leopard frogs. Chronic EMG electrodes were implanted for periods of 7–10 days. This permitted us to record EMG activities during both hopping and swimming from the same electrode, allowing a direct comparison of the timing and amplitudes of muscle activity between the two behaviors. We could then relate these activities to the kinematics of locomotion. In both behaviors, all three extensors were synchronously activated 30–50 ms before limb extension began. However, the hip extensor turned on relatively earlier in hopping than in swimming when on time was expressed as percent of stride. The hip and knee extensors were activated relatively longer in hopping and the ankle extensor relatively longer in swimming. The amplitudes of the rectified, integrated EMG signals were roughly twice as large in hopping as in swimming for all three muscles, supporting the notion that propulsion in hopping requires more force than in swimming. The EMG burst durations differed little between the muscles or, in relative duration, between the behaviors. As has been found in other quadrupeds, the EMG bursts began before visible movement and ceased at or before hindlimb extension was completed. In our animals, however, we found a consistent, low level (10–30% of maximum amplitude) of EMG activity that continued 60–200 ms past the end of the burst and into the suspension periods in both hopping and swimming. We hypothesize that this unusual activity may be present in frogs so that the hind limb remains aero(hydro)dynamically stable as the frog arches through its leap or glides in swimming following completed limb extension. Thus, the timing and pattern of the EMG bursts are consistent with those present in other tetrapods and support conservatism of neural control. However, the prolonged low-level activity suggests flexibility in the control pattern and variation according to specific behaviors. © 1996 Wiley-Liss, Inc.     

Partial inhibition of sarcoplasmic reticulum ca release evokes long-lasting ca release events in ventricular myocytes: role of luminal ca in termination of ca release

In cardiac myocytes, local sarcoplasmic reticulum (SR) Ca depletion during Ca sparks is believed to play an important role in the termination of SR Ca release. We tested whether decreasing the rate of SR Ca depletion by partially inhibiting SR Ca release channels (ryanodine receptors) delays Ca spark termination. In permeabilized cat ventricular myocytes, 0.7 mM tetracaine caused almost complete Ca spark inhibition followed by a recovery significantly below control level. The recovery was associated with increased SR Ca load and increased Ca spark duration. Additionally, SR Ca release events lasting several hundred milliseconds occurred consistently. These events had a significantly lower initial Ca release flux followed by a stable plateau, indicating delayed release termination and maintained SR Ca load. Increasing SR Ca load (without inhibiting SR Ca release rate) or decreasing SR Ca release rate (without increasing SR Ca load) both induced only a small increase in spark duration. These results show that the combination of decreased release flux and increased SR Ca load has synergistic effects and exerts major changes on the termination of Ca release events. Long-lasting Ca release events may originate from highly interconnected release junctions where Ca diffusion from neighboring sites partially compensates Ca depletion, thereby delaying SR Ca-dependent termination. Eventually, these events terminate by luminal Ca-independent mechanisms, such as inactivation, adaptation, or stochastic attrition.     

FGF negatively regulates muscle membrane extension in Caenorhabditis elegans

Striated muscles from Drosophila and several vertebrates extend plasma membrane to facilitate the formation of the neuromuscular junction (NMJ) during development. However, the regulation of these membrane extensions is poorly understood. In C. elegans, the body wall muscles (BWMs) also have plasma membrane extensions called muscle arms that are guided to the motor axons where they form the postsynaptic element of the NMJ. To investigate the regulation of muscle membrane extension, we screened 871 genes by RNAi for ectopic muscle membrane extensions (EMEs) in C. elegans. We discovered that an FGF pathway, including let-756(FGF), egl-15(FGF receptor), sem-5(GRB2) and other genes negatively regulates plasma membrane extension from muscles. Although compromised FGF pathway activity results in EMEs, hyperactivity of the pathway disrupts larval muscle arm extension, a phenotype we call muscle arm extension defective or MAD. We show that expression of egl-15 and sem-5 in the BWMs are each necessary and sufficient to prevent EMEs. Furthermore, we demonstrate that let-756 expression from any one of several tissues can rescue the EMEs of let-756 mutants, suggesting that LET-756 does not guide muscle membrane extensions. Our screen also revealed that loss-of-function in laminin and integrin components results in both MADs and EMEs, the latter of which are suppressed by hyperactive FGF signaling. Our data are consistent with a model in which integrins and laminins are needed for directed muscle arm extension to the nerve cords, while FGF signaling provides a general mechanism to regulate muscle membrane extension.     

The sarcoplasmic reticulum and sarcolemma together form a passive Ca2+ trap in colonic smooth muscle

In smooth muscle, active Ca(2+) uptake into regions of sarcoplasmic reticulum (SR) which are closely apposed to the sarcolemma has been proposed to substantially limit the increase in the cytoplasmic Ca(2+) concentration ([Ca(2+)](c)) following Ca(2+) influx, i.e. the 'superficial buffer barrier hypothesis'. The present study has re-examined this proposal. The results suggest that the SR close to the sarcolemma acts as a passive barrier to Ca(2+) influx limiting [Ca(2+)](c) changes; for this, SR Ca(2+) pump activity is not required. In single voltage-clamped colonic myocytes, sustained opening of the ryanodine receptor (RyR) (and depletion of the SR) using ryanodine increased the amplitude of depolarisation-evoked Ca(2+) transients and accelerated the rate of [Ca(2+)](c) decline following depolarisation. These results could be explained by a reduction in the Ca(2+) buffer power of the cytosol taking place when RyR are opened (i.e. the SR is 'leaky'). Indeed, determination of the Ca(2+) buffer power confirmed it was reduced by approximately 40%. Inhibition of the SR Ca(2+) pump (with thapsigargin) also depleted the SR of Ca(2+) but did not reduce the Ca(2+) buffer power or increase depolarisation-evoked Ca(2+) transients and slowed (rather than accelerated) Ca(2+) removal. However, thapsigargin prevented the ryanodine-induced increase in [Ca(2+)](c) decline following depolarisation. Together, these results suggest that when the SR was rendered 'leaky' (a) more of the Ca(2+) entering the cell reached the bulk cytoplasm and (b) Ca(2+) was removed more quickly at the end of cell activation. Under physiological circumstances in the absence of blocking drugs, it is proposed that the SR limits the [Ca(2+)](c) increase following influx without the need for active Ca(2+) uptake. The SR and sarcolemma may form a passive physical barrier to Ca(2+) influx, a Ca(2+) trap, which limits the [Ca(2+)](c) rise occurring during depolarisation by about 50% and from which the ion only slowly escapes into the main part of the cytoplasm.     

Modification of subcellular organelles in pressure-overloaded heart by etomoxir, a carnitine palmitoyltransferase I inhibitor.

To examine the signals regulating cardiac growth and molecular structure of subcellular organelles, cardiac hypertrophy was induced in rats by constriction of the abdominal aorta for 12-13 wk or by treatment with a carnitine palmitoyltransferase I inhibitor, etomoxir (12-15 mg/kg body wt) for 12-13 wk. In contrast to pressure overload, etomoxir redistributed the myosin isozyme population from V3 to V1 and increased the sarcoplasmic reticulum (SR) Ca(2+)-stimulated ATPase activity. When rats with pressure-overloaded hearts were treated with etomoxir, the cardiac hypertrophy was increased whereas the shift in myosin isozymes from V1 to V3 was prevented and the depression in SR Ca(2+)-stimulated ATPase activity was reversed. Plasma thyroid hormone and insulin concentrations were not altered but triglyceride concentrations were reduced in etomoxir-treated rats with pressure overload. The data demonstrate a dissociation between cardiac muscle growth and changes in subcellular organelles and indicate that a shift in myocardial substrate utilization may represent an important signal for molecular remodeling of the heart.