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Biomedical subjects

J N Howell

Publications and source records attributed to J N Howell.

32 records · Page 2Linked to original sources

Inhibition of tetanus tension by elevated extracellular calcium concentration.

Extracellular [Ca2+] in the range of 5-20 mM produces a concentration-dependent reversible reduction in tetanus tension in single frog skeletal muscle fibers. Both peak tension and ability to sustain tension during tetanus is reduced. The effect is unrelated to osmotic effects and independent of stimulation frequency in the range 100-200 Hz. The effect occurs both at 8 and 24 degrees C. Tetanus tension is most strongly inhibited by elevated extracellular [Ca2+] at short muscle lengths, but the effect can be seen at all lengths. Microelectrode recordings during tetanus indicate that action potentials remain undiminished in amplitude and duration throughout the tetanus. The evidence suggests that the inhibition results from a failure of action potentials propagation within the transverse tubular system.

Action Potentials↗

Population screening for the human adult lactase phenotypes with a multiple breath version of the breath hydrogen test.

Lactose tolerance tests with conventional blood glucose determination and with breath hydrogen analysis after storage of breath samples in aluminium aerosol cans were simultaneously performed in 60 healthy adult subjects. Both tests were equally reliable in the diagnosis of the lactase phenotype in healthy persons. In subjects with decreased glucose metabolism the breath hydrogen test seems to be more reliable than the blood glucose test. Provisions for storing breath samples for up to several weeks, avoidance of invasive procedures and insensitivity of glucose absorbed during the test make the present version of the lactose tolerance test with breath hydrogen determination particularly suitable for population studies.

Adult↗

Intestinal disaccharidase activities and activity ratios in a group of 60 adult German subjects.

Lactase, maltase and sucrase activities were determined in samples of jejunal mucosa obtained by suction biopsy from 60 healthy adult German males. Primary adult hypolactasia ("lactase deficiency") was found in 8 subjects (13%). Maltase:lactase and sucrase:lactase activity ratios were significantly higher in post-weaning hypolactasia than in adult lactase persistence. Sources of variation in disaccharidase activities measured in biopsy tissue homogenates are discussed.

Adult↗

The capacitance of skeletal muscle fibers in solutions of low ionic strength.

The capacitance of skeletal muscle fibers was measured by recording with one microelectrode the voltage produced by a rectangular pulse of current applied with another microelectrode. The ionic strength of the bathing solution was varied by isosmotic replacement of NaCl with sucrose, the [K] [Cl] product being held constant. The capacitance decreased with decreasing ionic strength, reaching a value of some 2 microF/cm(2) in solutions of 30 mM ionic strength, and not decreasing further in solutions of 15 mM ionic strength. The capacitance of glycerol-treated fibers did not change with ionic strength and was also some 2 microF/cm(2). It seems likely that lowering the ionic strength reduces the capacitance of the tubular system (defined as the charge stored in the tubular system), and that the 2 microF/cm(2) which is insensitive to ionic strength is associated with the surface membrane. The tubular system is open to the external solution in low ionic strength solutions since peroxidase is able to diffuse into the lumen of the tubules. Twitches and action potentials were also recorded from fibers in low ionic strength solutions, even though the capacitance of the tubular system was very small in these solutions. This finding can be explained if there is an action potential-like mechanism in the tubular membrane.

Action Potentials↗

A theoretical analysis of the capacitance of muscle fibers using a distributed model of the tubular system.

A model is developed to predict the changes in total capacitance (i.e. total charge stored divided by surface membrane potential) of the tubular system of muscle fibers. The tubular system is represented as a punctated disc and the area of membrane across which current flows is represented as a punctated annulus, the capacitance of the muscle fiber being proportional to this area. The area can be determined from a distributed model of the tubular system, in which the only resistance to radial current flow is presumed to be in the lumen of the tubules. Calculations are made of the variation of capacitance expected as the conductivity of the bathing solution is varied. These calculations include the effects of fixed charge in the tubular lumen and the effects of changes in the shape and volume of the tubular system in solutions of low conductivity. The calculated results fail to fit comparable experimental data, although they do qualitatively account for the known variation of the radial spread of contraction with conductivity of the bathing medium. It is pointed out that the existence of a significant "access resistance" at the mouth of the tubules might explain the discrepancy between theory and experiment.

Electrophysiology↗

The maintenance of resting potentials in glycerol-treated muscle fibres.

1. A modification of a previously published method for the disruption of the T-tubules of frog skeletal muscle is described. The modification permits the disruption of the T-tubules without the decline in resting potentials which was reported previously.2. The method for the disruption of the T-tubules involves the washout of glycerol following loading in a 400 mM glycerol Ringer solution. The modification consists of elevating the concentration of divalent cations in the Ringer used for glycerol washout.3. The optimum concentrations are 5 mM-Ca(2+) and 5 mM-Mg(2+) added as their chloride salts. Neither 10 mM-Ca(2+) nor 10 mM-Mg(2+) are as effective as the combination of each at 5 mM. Other concentrations gave less satisfactory results.4. The use of the modified technique provides a preparation which maintains 85-90 mV resting potentials for up to 6 or 8 hr but which will not contract in response to membrane depolarization.

Animals↗

A lesion of the transverse tubules of skeletal muscle.

1. A method is described by which a selective lesion can be made in vitro in the transverse tubules of frog skeletal muscle.2. The method consists of exposing the muscle for 1 hr or more to a buffered salt solution made hypertonic by the inclusion of 400 mM glycerol and then returning the muscle to an isotonic salt solution. The lesion is induced during the washout of the glycerol.3. Electron micrographs reveal that the lesion consists of a rearrangement of the T-system membranes in such a way that the continuity of the tubules is lost. The membranes appear to coalesce into large vesicles scattered irregularly throughout the sarcoplasm.4. The glycerol treatment results in a depression of the resting potential of up to 30 mV. The treated fibres are depolarized by high concentrations of K as are normal muscle fibres.5. T-tubule lesioned fibres are unable to respond mechanically either to electrical stimulation or to elevated K but they do contract in the presence of caffeine and relax when the caffeine is removed.6. Problems concerning the variability of the procedure are presented and certain considerations concerning the mechanism of the effect are discussed.

Animals↗