Molecular insights into excitation-contraction coupling.
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Animals↗
Biomedical subjects
B A Adams
Publications and source records attributed to B A Adams.
A novel calcium current in dysgenic skeletal muscle.
The whole-cell patch-clamp technique was used to study voltage-dependent calcium currents in primary cultures of myotubes and in freshly dissociated skeletal muscle from normal and dysgenic mice. In addition to the transient, dihydropyridine (DHP)-insensitive calcium current previously described, a maintained DHP-sensitive calcium current was found in dysgenic skeletal muscle. This current, here termed ICa-dys, is largest in acutely dissociated fetal or neonatal dysgenic muscle and also in dysgenic myotubes grown on a substrate of killed fibroblasts. In dysgenic myotubes grown on untreated plastic culture dishes, ICa-dys is usually so small that it cannot be detected. In addition, ICa-dys is apparently absent from normal skeletal muscle. From a holding potential of -80 mV. ICa-dys becomes apparent for test pulses to approximately -20 mV and peaks at approximately +20 mV. The current activates rapidly (rise time approximately 5 ms at 20 degrees C) and with 10 mM Ca as charge carrier inactivates little or not at all during a 200-ms test pulse. Thus, ICa-dys activates much faster than the slowly activating calcium current of normal skeletal muscle and does not display Ca-dependent inactivation like the cardiac L-type calcium current. Substituting Ba for Ca as the charge carrier doubles the size of ICa-dys without altering its kinetics. ICa-dys is approximately 75% blocked by 100 nM (+)-PN 200-110 and is increased about threefold by 500 nM racemic Bay K 8644. The very high sensitivity of ICa-dys to these DHP compounds distinguishes it from neuronal L-type calcium current and from the calcium currents of normal skeletal muscle. ICa-dys may represent a calcium channel that is normally not expressed in skeletal muscle, or a mutated form of the skeletal muscle slow calcium channel.
Animals↗
Temperature and synaptic efficacy in frog skeletal muscle.
1. Intracellular recording and voltage-clamp techniques were used to measure synaptic efficacy and the safety factor for neuromuscular transmission in frog skeletal muscle. All measurements were made in normal Ringer solution, in the absence of presynaptic or postsynaptic blocking agents. 2. Over a broad temperature range (10-30 degrees C), a small percentage of sartorius fibres (about 6%) could be found which produced only subthreshold end-plate potentials and no action potential in response to single, supramaximal nerve shock. At lower temperatures the proportion of such fibres increased; 42% of the fibres had subthreshold transmission at 5 degrees C, and 59% were subthreshold at 2.5 degrees C. 3. Threshold current, measured by intracellularly injecting short pulses of depolarizing current at end-plate regions, was independent of temperature between 2.5 and 20 degrees C. Thus, the reduced synaptic efficacy observed at low temperatures was not due to decreased electrical excitability of the postsynaptic membrane. 4. The amplitude of evoked end-plate currents (EPCs) decreased with cooling. At temperatures below 10 degrees C, the evoked EPCs at many end-plates were too small to initiate action potentials. The decline in EPC amplitude was due to three factors: a decrease in the amplitude of single quantum currents (MEPCs), an increase in the temporal dispersion of transmitter release, and (below 5 degrees C) a decrease in quantal content. 5. The safety factor for neuromuscular transmission decreased dramatically as temperature was lowered. At 30 degrees C average safety factor was large and positive (540 nA), but at 2.5 degrees C it was negative (-78 nA). 6. The quantal content of evoked transmitter release was independent of temperature change between 5 and 30 degrees C, the average value over this range being 180. However, at temperatures below 5 degrees C, quantal content fell off sharply (average value = 37). 7. The thermal independence of transmitter release may be an important mechanism in allowing poikilothermic animals to maintain physiological function over a wide range of body temperatures.
Action Potentials↗
The danger of an inadequate water intake during prolonged exercise. A novel concept re-visited.
To prevent thermal injuries during distance running, the American College of Sports Medicine proposes that between 0.83 and 1.65 l of water should be ingested each hour during prolonged exercise. Yet such high rates of fluid intake have been reported to cause water intoxication. To establish the freely-chosen rates of fluid intake during prolonged competitive exercise, we measured fluid intake during, body weight before and after, and rectal temperature after competition in a total of 102 runners and 91 canoeists competing in events lasting from 170-340 min. Fluid intakes during competition ranged from 0.29-0.62 l.h-1; rates of water loss ranged from 0.69-1.27 l.h-1 in the runners; values were lower in the canoeists. Mean post-race rectal temperatures ranged from 38.0-39.0 degrees C. There was no relationship between the degree of dehydration and post-race rectal temperature. We conclude that hyperthermia is uncommon in prolonged competitive events held in mild environmental conditions, and that exercise intensity, not the level of dehydration, is probably the most important factor determining the postexercise rectal temperature. During prolonged exercise in mild environmental conditions, a fluid intake of 0.5 l.h-1 will prevent significant dehydration in the majority of athletes.
Adolescent↗
Legionella bozemanii pneumonia in an immunocompromised patient.
Legionella bozemanii, a rare cause of pneumonia, has a predilection for patients with impaired cellular immunity and underlying disease. We report the 12th culture-proven case of this infection, acquired in the community by a patient undergoing chemotherapy for chronic lymphocytic leukemia. The diagnosis was established when studies of bronchoalveolar lavage fluid produced a positive reaction with species-specific fluorescent antibody and growth on selective culture media. Although erythromycin was administered within 48 hours after the initial examination, the clinical condition did not improve substantially until rifampin was added to the antimicrobial regimen.
Aged↗
Potassium excretion in renal failure in the rat: the role of distal tubule flow and aldosterone.
1. This study examines the contribution of an increased distal tubule flow and of aldosterone to the handling of a potassium load in conscious rats with renal failure induced by subtotal nephrectomy or by gentamicin on a control of high K+ diet. 2. Glomerular filtration rate was reduced by subtotal nephrectomy to 40% and by gentamicin treatment to 60% of control. Subtotal nephrectomy induced significant hypertrophy of glomeruli and proximal and distal tubules, but gentamicin did not. Both experimental groups had a normal iothalamate space and plasma potassium after a 20 h fast. 3. Two hours after an acute KCl load rats with renal failure excreted less potassium than control rats. There was also a lesser natriuretic effect of KCl in the renal failure groups. 4. A high K+ diet, given for 5-7 days, increased excretion of an acute KCl load in control rats and rats with renal failure. 5. (UNaV + UKV) was used as an estimate of distal tubule flow. Potassium excretion, related to distal tubule flow, was similar in the renal failure and control rats when on the same diet. This is consistent with potassium excretion being strongly, but not necessarily solely, dependent on distal flow. 6. Adrenalectomy reduced, and aldosterone restored, potassium excretion in the renal failure and control groups. This suggests a role for aldosterone in excretion of an acute potassium load with this degree of renal failure.
Acute Kidney Injury↗
In vivo estimation of changes in distal tubule flow and their role in dexamethasone-induced kaliuresis in control and potassium-adapted rats.
The aim of this study was to determine whether the kaliuresis associated with glucocorticoids is due to a direct tubular action or is secondary to effects of glucocorticoids on distal tubule flow. A whole kidney technique was used to avoid the problem, inherent in microperfusion and micropuncture studies, of deciding whether (all) the appropriate nephron segment(s) are being studied. The method used was to determine the best whole kidney measure of distal tubule flow (the independent variable) by correlating this with the dependent variable (potassium excretion, corrected for differences in plasma potassium, UkV/PIK+) in conscious intact and adrenalectomized control and potassium-adapted rats. After an intragastric potassium chloride load, the correlation of UkV/PIK+ with UkV + UNaV was better than with either UNaV or UV, as measures of distal tubule flow. From the relationship a measure of potassium excretion independent of distal tubule flow can thus be calculated as UkV/PIK+ divided by (UkV + UNaV), defined as UK#. Measurement of UK# clearly demonstrates decreases in potassium excretion with adrenalectomy and increases in potassium excretion with aldosterone and in the potassium-adapted rat, consistent with described changes in potassium secretion. In contrast, with dexamethasone treatment, whilst there was an increase in UkV and UkV/PIK+, there was no change in UK# either in the control of potassium-adapted rats. These results suggest that the kaliuretic effect of dexamethasone cannot be attributed to direct tubular effects of glucocorticoids but rather can be explained by its effect on distal tubule flow.
Adaptation, Physiological↗
Aldosterone is a physiologically significant kaliuretic hormone.
To study the role of aldosterone in the short-term control of potassium excretion, rats were gavaged with a liquid diet containing 10-20% of their daily caloric and potassium intake, with a range of sodium intakes. Levels of (effective) aldosterone at the time of gavage were manipulated by administration of spironolactone, aldosterone, and adrenalectomy. Urinary sodium, potassium, and creatinine excretion were measured in conscious unrestrained rats for 2 h after the food load, and then blood was collected for measurement of plasma potassium, aldosterone, and renin activity. Potassium excretion was dependent on both dietary potassium and a minimum dietary sodium content. Potassium excretion was reduced by spironolactone and adrenalectomy and increased by acute aldosterone treatment in most dietary groups. These results strongly suggest that the ambient levels of aldosterone are important in determining potassium excretion following food ingestion. Plasma aldosterone was higher with the higher potassium and lower sodium content diets. Changes in plasma aldosterone, with variations in dietary potassium or sodium, suggest a role for aldosterone in subsequent potassium excretion.
Adrenalectomy↗
Thermal dependence of passive electrical properties of lizard muscle fibres.
1. The thermal dependence of passive electrical properties was determined for twitch fibres from the white region of the iliofibularis (IF) muscle of Anolis cristatellus (15-35 degrees C) and Sceloporus occidentalis (15-40 degrees C), and for twitch fibres from the white (15-45 degrees C) and red (15-40 degrees C) regions of the IF of Dipsosaurus dorsalis. These species differ in thermal ecology, with Anolis being the least thermophilic and Dipsosaurus the most thermophilic. 2. Iliofibularis fibres from the three species reacted similarly to changing temperature. As temperature was increased, input resistance (Rin) decreased (average R10 = 0.7), length constant (L) decreased (average R10 = 0.9), time constant (tau) decreased (average R10 = 0.8), sarcoplasmic resistivity (Rs) decreased (average R10 = 0.8) and apparent membrane resistance (Rm) decreased (average R10 = 0.7). In contrast, apparent membrane capacitance (Cm) increased with increasing temperature (average R10 = 1.3). 3. Rin, L, tau and apparent Rm were lowest in fibres from Anolis (the least thermophilic species) and highest in fibres from Dipsosaurus (the most thermophilic species). Anolis had the largest and Dipsosaurus the smallest diameter fibres (126 and 57 micron, respectively). Apparent Cm was highest in fibres from Sceloporus, which had fibres of intermediate diameter (101 micron). Rs did not differ significantly among species. 4. The effect of temperature on the passive electrical properties of these lizard fibres was similar to that reported for muscle fibres from other ectothermic animals (crustaceans, insects, fish and amphibians) but qualitatively different from that reported for some mammalian (cat tenuissimus, goat intercostal) fibres. The changes that occur in the passive electrical properties render the fibres less excitable as temperature increases.
Animals↗
Potassium excretion by the isolated perfused kidney from the potassium-adapted rat.
Adaptation to a high potassium diet leads to an enhanced ability to excrete an acute potassium load. The aim of this study was to examine whether the enhanced kaliuretic ability is an intrinsic renal adaptation or is secondary to extrarenal mediators such as aldosterone. Kidneys from control rats and rats on a high potassium diet were isolated and perfused in a cell-free medium (glomerular filtration rate 0.5 ml/min, fractional sodium reabsorption 95%). Feeding in the 24 h prior to perfusion had a profound effect on fractional K+ excretion in rats on high K+ (fed 1.4 +/- 0.11, fasted 0.70 +/- 0.07) but not in control (fed 0.59 +/- 0.05, fasted 0.64 +/- 0.05) rats. After feeding but not fasting, rats on high K+ had a greater fractional K+ excretion than control K+ rats. Spironolactone inhibited fractional K+ excretion in fed rats on high K+ but not in control rats (high K+ 1.45 +/- 0.18, high K+ + spironolactone 0.95 +/- 0.15; control 0.59 +/- 0.05, control + spironolactone 0.46 +/- 0.02). Although these experiments do not exclude an intrinsic renal adaptation in potassium excretion, a major component of the increased potassium excretion relates to the increased potassium intake, probably mediated via aldosterone.
Adaptation, Physiological↗
Production and excretion of dopamine by the isolated perfused rat kidney.
Renal catecholamine concentrations and urinary dopamine excretion from the isolated perfused kidney were measured in intact and peripherally sympathectomized rats. Urinary dopamine excretion was not diminished by sympathectomy, was increased by l-dopa (but not tyrosine or dopamine 4-O-sulphate) in the perfusate and was virtually abolished by prior treatment with the dopa decarboxylase inhibitor, carbidopa. These results confirm the importance of renal extraneuronal dopamine production, from circulating l-dopa, as a contributor to urinary dopamine excretion.
Animals↗
Acquired divergent strabismus: presumed metastatic gastric carcinoma to the medial rectus muscle.
A patient with rapidly progressive metastatic gastric carcinoma developed diplopia and diminished adduction of the right eye. The right medial rectus muscle belly was enlarged, as shown by computed tomography. This case is unusual, because gastric carcinoma comprises only 1% of orbital metastases and less than 5% of all orbital metastases localize to extraocular muscle.
Carcinoma↗