Octopamine stabilizes conduction reliability of an unmyelinated axon during hypoxic stress.

Mechanisms that could mitigate the effects of hypoxia on neuronal signaling are incompletely understood. We show that axonal performance of a locust visual interneuron varied depending on oxygen availability. To induce hypoxia, tracheae supplying the thoracic nervous system were surgically lesioned and action potentials in the axon of the descending contralateral movement detector (DCMD) neuron passing through this region were monitored extracellularly. The conduction velocity and fidelity of action potentials decreased throughout a 45-min experiment in hypoxic preparations, whereas conduction reliability remained constant when the tracheae were left intact. The reduction in conduction velocity was exacerbated for action potentials firing at high instantaneous frequencies. Bath application of octopamine mitigated the loss of conduction velocity and fidelity. Action potential conduction was more vulnerable in portions of the axon passing through the mesothoracic ganglion than in the connectives between ganglia, indicating that hypoxic modulation of the extracellular environment of the neuropil has an important role to play. In intact locusts, octopamine and its antagonist, epinastine, had effects on the entry to, and recovery from, anoxic coma consistent with octopamine increasing overall neural performance during hypoxia. These effects could have functional relevance for the animal during periods of environmental or activity-induced hypoxia.

Acoustic startle/escape reactions in tethered flying locusts: motor patterns and wing kinematics underlying intentional steering.

We simultaneously recorded flight muscle activity and wing kinematics in tethered, flying locusts to determine the relationship between asymmetric depressor muscle activation and the kinematics of the stroke reversal at the onset of wing depression during attempted intentional steering manoeuvres. High-frequency, pulsed sounds produced bilateral asymmetries in forewing direct depressor muscles (M97, 98, 99) that were positively correlated with asymmetric forewing depression and asymmetries in stroke reversal timing. Bilateral asymmetries in hindwing depressor muscles (M127 and M128 but not M129) were positively correlated with asymmetric hindwing depression and asymmetries in the timing of the hindwing stroke reversal; M129 was negatively correlated with these shifts. Hindwing depressor asymmetries and wing kinematic changes were smaller and shifted in opposite direction than corresponding measurements of the forewings. These findings suggest that intentional steering manoeuvres employ bulk shifts in depressor muscle timing that affect the timing of the stroke reversals thereby establishing asymmetric wing depression. Finally, we found indications that locusts may actively control the timing of forewing rotation and speculate this may be a mechanism for generating steering torques. These effects would act in concert with forces generated by asymmetric wing depression and angle of attack to establish rapid changes in direction.

Auditory-evoked evasive manoeuvres in free-flying locusts and moths.

We presented free-flying locusts (Locusta migratoria L.) with sounds that varied in temporal structure and carrier frequency as they flew toward a light source in a flight room under controlled temperature and light conditions. Previous studies have shown tethered locusts react more often to trains of 30-kHz pulses than to pulse trains below 10 kHz. Further, this acoustic startle response has been suggested to function in bat-avoidance. We expected free-flying locusts to respond similarly; however, we found locusts responded to all sounds we presented, not just high-frequency, "bat-like" sounds. Response rates of turns, loops, and dives varied from 6% to 26% but were statistically independent of carrier frequency and/or pulse structure. Free-flying moths and tethered locusts were tested using a subset of our acoustic stimuli under the same temperature and light conditions as the free-flying locusts. Moth responses were carrier frequency dependent as were responses of tethered locusts positioned along the flight path observed in our free-flight trials. All responses were unaffected by a 90% reduction in room light. We conclude that locusts possess an acoustic startle response evocable in free flight, however, free-flying locusts do not show the same discrimination observed in tethered locusts under similar conditions.

Role of weight loss and polyunsaturated fatty acids in improving metabolic fitness in moderately obese, moderately hypertensive subjects.

OBJECTIVE: While the exact regulatory interactions between blood pressure (BP) and obesity are not completely understood, weight loss provides an alternative to pharmacological treatment of hypertension. The intent of this repeated measures study of mild-moderate hypertensive, moderately obese subjects (34 females/18 males) was to determine if the reduction in BP following weight loss could be further affected by modifying the fatty acid (FA) composition of the hypocaloric diet. METHODS: BP, insulin sensitivity (Si), and lipid parameters were assessed before and after a 10-week calorie-restricted period. Subjects were randomized to one of three dietary groups differing in FA composition. Reduced body weight was maintained for a further 4 weeks and body composition assessment, BP and heart rate measurements were repeated. RESULTS: Weight loss (10%) in obese hypertensive subjects resulted in substantial improvements in BP, Si and lipid profile. There was no additional effect on the reduction in BP by the type of FA consumed in the diet. Following weight loss, there was a trend for omega-3 FAs to have a protective effect on fat-free mass loss (compared to omega-6 FA Group and saturated FA Group) and a trend to further enhance Si. There were significant improvements in circulating lipid profiles independent of the dietary FA intervention following the weight loss. The improvements in BP and body composition were maintained during the weight-loss maintenance period. The type of fat consumed had minor differential effects on some of the measured metabolic outcomes. CONCLUSION: These results provide strong support for modest weight loss as a treatment for hypertension.

Contrasting effects of vasodilators on blood pressure and sodium balance in the hypertension of autonomic failure.

Supine hypertension, which is very common in patients with autonomic failure, limits the use of pressor agents and induces nighttime natriuresis. In 13 patients with severe orthostatic hypotension due to autonomic failure (7 women, 6 men, 72 +/- 3 yr) and supine hypertension, the effect of 30 mg nifedipine (n = 10) and 0.025 to 0.2 mg/h nitroglycerin patch (n = 11) on supine BP, renal sodium handling, and orthostatic tolerance was determined. Medications were given at 8 p.m.; patients stood up at 8 a.m. Nitroglycerin was removed at 6 a.m. Compared with placebo, nifedipine and nitroglycerin decreased systolic BP during the night by a maximum of 37 +/- 9 and 36 +/- 10 mmHg, respectively (P < 0.01). At 8 a.m., supine systolic BP was 23 +/- 7 mmHg lower with nifedipine than with placebo (P < 0.05), but was similar with nitroglycerin and placebo. Sodium excretion during the night was not reduced with nitroglycerin (0.13 +/- 0.02 mmol/mg creatinine [Cr] versus 0.15 +/- 0.03 mmol/mg Cr with placebo), but it was increased with nifedipine (0.35 +/- 0.06 mmol/mg Cr versus 0.13 +/- 0.02 mmol/mg Cr with placebo, P < 0.05). Nifedipine but not nitroglycerin worsened orthostatic hypotension in the morning. It is concluded that nifedipine and transdermal nitroglycerin are effective in controlling supine hypertension in patients with autonomic failure. However, nifedipine has a prolonged depressor effect and worsens orthostatic hypotension in the morning. The decrease in pressure natriuresis that would be expected with the substantial decrease in BP obtained with nitroglycerin and nifedipine may be offset by a direct effect of both drugs on renal sodium handling.

Hydrophobic amino acid residues of human anticoagulation protein C that contribute to its functional binding to phospholipid Vesicles.

The contributions to functional phospholipid (PL) binding of the cluster of amino acid side chains of human protein C (PC) comprising F4, L5, and L8 have been assessed by construction of mutants of PC and activated protein C (APC) designed wherein a hydrophilic side chain replaced the wild-type hydrophobic groups at these positions. The PL-dependent plasma-based anticoagulant activities of [F4Q]-r-APC and [L8Q]r-APC were severely reduced to 5% and < 2%, respectively, of wild-type r-APC. Activity losses of the mutants toward inactivation of coagulation factor VIII, measured in the complete in vitro tenase system, have also been observed. As evidenced through Ca(2+)-induced intrinsic fluorescence changes, both [F4Q]r-PC and [L8Q]r-PC were able to adopt Ca(2+)-dependent conformations that appeared similar to that of wtr-PC, ruling out shortcomings associated with such Ca(2+)-induced transitions as the basis for their anticoagulant activity losses. However, despite this, [L8Q]r-PC showed greatly defective macroscopic binding properties to PL vesicles, as did to a lesser extent [F4Q]r-PC. These findings were similar to those reported previously for [L5Q]r-PC/APC [Zhang, L., & Castellino, F. J. (1994) J. Biol. Chem. 269, 3590-3595]. We thus propose that the PL-dependent activity losses of these mutants are related to their suboptimal binding to PL or to their misorientation on the PL surface leading to poor alignment of the active sites of the r-APC mutants with the complementary cleavage sites on fVIII/fVIIIa and fV/fVa.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitral anular calcification in chronic renal failure.

In order to determine the incidence and pathogenesis of mitral anular calcification (MAC) in chronic renal failure, we analyzed biochemical, hemodynamic and echocardiographic data in 168 patients on long-term hemodialysis. Mitral anular calcification is more common in patients with chronic renal failure than in other patients of similar age. Its pathogenesis appears to be due to abnormal calcium-phosphorus homeostasis in the setting of secondary hyperparathyroidism. Hypertension did not appear to be an important etiologic factor in our patients. Meticulous control of hyperphosphatemia would appear to be the most important therapeutic measure in preventing this complication.

Firing between two spike thresholds: implications for oscillating lobster interneurons.

An identified interneuron in the lobster commissural ganglia fires spikes only between membrane potential values of -60 and -30 millivolts. The membrane potential of this neuron can also oscillate, and interaction between these two properties has important implications in determining the firing pattern of the neuron itself and the modalities of driving of a distant postsynaptic neuron.

A corollary discharge of total foregut motor activity is monitored by a single interneurone in the lobster Homarus gammarus.

1. In Homarus, an identified interneurone (the L cell), which possesses the largest cell body in the commissural ganglion and projects to the brain, exhibits a complex firing pattern (Fig. 2 a). 2. It is shown that the L cell discharges with each of the 4 pattern generators of the stomatogastric nervous system which organize the rhythmic motor activity of the foregut (Fig. 2 b-e). 3. Manipulation of the membrane potential of the L cell does not induce any change in the 4 rhythms (Fig. 3), and it is concluded that the L cell is driven by the 4 pattern generators. 4. The functional meaning of this complex corollary discharge of the total foregut motor activity is discussed.

Control of rhythmic behaviour by a hierarchy of linked oscillators in crustacea.

In Homarus, the central pattern generators for the rhythmic motor activities of the gastric teeth and the pyloric chamber are located in the stomatogastric ganglion. It is shown that independent gastric and pyloric oscillators are also contained in higher nervous centres (the commissural ganglia) and provide a phasic rhythmic input to the stomatogastric pattern generators. This demonstrates that rhythmic behaviour can be organized by a hierarchy of linked oscillators each capable of producing the rhythm.

Oesophageal sensors and their modulatory influence on oesophageal peristalsis in the lobster, Homarus gammarus.

The musculature and innervation of the oesophagus of Homarus gammarus are described as a prerequisite to studies on the mechanisms and control of food ingestion. Of particular interest are two paired sensors (the anterior and posterior oesophageal sensors) which are bilaterally situated at the oesophageal-cardiac sac valve. These are similar to contact chemoreceptors previously described in insects and are classified as such on morphological grounds and with indirect electrophysiological evidence. Oesophageal peristalsis is effected by the coordinated contraction of the Oesophageal musculature. This is controlled by rhythmical bursting neuronal activity, which can be recorded from the nerve trunks in the area. A characteristic burst recorded from the superior oesophageal nerve is used as an indication of oesophageal dilatation during peristalsis for studies on the feedback effects of the oesophageal sensors. Electrical and chemical stimulation of the posterior oesophageal sensors can initiate and increase the frequency of oesophageal peristalsis, while stimulation of the anterior oesophageal sensors can slow and terminate oesophageal peristalsis. The results are discussed and a model presented of the role of the oesophageal sensors in feeding.

The structure and function of the labrum in the lobster Homarus gammarus (L.).

The labrum of decapod crustaceans is a soft lobe overhanging the mouth. The labral skeleton, musculature and innervation of Homarus gammarus are described. There are three bilateral groups of sensory neurons innervating the floor, lobe and lateral walls of the labrum. These are probably responsible for the phasic afferent activity that can be recorded from the inner labral nerve on mechanical deformation of the labrum. The labrum undergoes rhythmical retraction-protraction movements during ingestion and is shown to be active during both mandibular activity and oesophageal peristalsis. Studies were made on the duration and frequency of labral "swallowing" activity. The role of the labrum in feeding is discussed.

The structure and function of thoracic exopodites in the larvae of the lobster Homarus gammarus (L.).

The first three larval stages of the lobster Homarus gammarus are pelagic swimming animals. A description is given of the exopodite apparatus of the thoracic appendages that provide lift and propulsive power in these stages. Setal arrangement and display provides greater surface area during power strokes. Musculature is peculiar to the exopodites and concerned with rotational movements of the appendage. Metachronal beating takes place with the segmental appendages moving in a variable sequence.