Search PubMed⌕ Search

Biomedical subjects

T M Butler

Publications and source records attributed to T M Butler.

At least 55 records · Page 3Linked to original sources
PubMed1986

Slowing of cross-bridge cycling in smooth muscle without evidence of an internal load.

We have tested whether the slowing in velocity of shortening that occurs in mammalian smooth muscle under conditions of high force output and dephosphorylated myosin light chains is due to an internal load presented by non- or slowly cycling cross bridges. The experimental design included stimulation of the rabbit taenia coli for 25 s under isometric conditions followed by 30 s of relaxation prior to the test stimulus. There was a large decrease in maximum velocity of shortening and chemical energy usage as well as a significantly decreased myosin light-chain phosphorylation response during the test stimulus even though active force developed to 90 +/- 4% of the original. The chemical energy cost of active external work production was not significantly different from that of the initial stimulation. There is, therefore, no energetic evidence for the dissipation of work against an internal load under conditions during which most of the force would be expected to be generated by latch bridges. We conclude that force maintenance with a low energy input and a slow velocity of shortening in mammalian smooth muscle represents a general slowing of the cross-bridge cycling rate rather than the appearance of a class of latch bridges that provide an internal load against which other cross bridges must operate.

Animals↗
PubMed1985

Phosphocreatinine, a high-energy phosphate in muscle, spontaneously forms phosphocreatine and creatinine under physiological conditions.

Phosphocreatinine undergoes the following spontaneous simultaneous reactions at pH 7.4 (0.02 M sodium phosphate and 120 mM KCl) and 38 degrees C. (Formula: see text) The first order rate constants are 0.046 h-1 (ka) and 0.048 h-1 (kb). There is a major effect of pH on the reactions such that at pH values higher than 7.4 phosphocreatine production predominates, while at pH values less than 7.4 creatinine is the major product. This along with titration data showing apparent pK values of about 3.0 and 7.5 for phosphocreatinine suggest that the dianionic form of phosphocreatinine is involved in the conversion to phosphocreatine, whereas the monoanionic form is exclusively converted to creatinine. Possible mechanisms to account for the reactivity of phosphocreatinine are discussed. Several lines of evidence suggest that the apparent Keq for phosphocreatine formation from phosphocreatinine is about 300 at pH 9.0 and about 70 at pH 7.0, and the delta G0' (pH 7.0) is-2.6 kcal/mol. The delta G0' (pH 7.0) for the hydrolysis of the phosphoryl bond in phosphocreatinine is-12.8 kcal/mol. The phosphocreatinine content of rabbit white skeletal muscle was measured to be 0.05 mumol/g, which is 0.4% of the phosphocreatine content. The in vitro experiments suggest that phosphohydrolysis of phosphocreatinine can account for a creatinine formation equal to 0.5% of the phosphocreatine content/day. We conclude that it is likely that a substantial fraction of the in vivo creatinine production from phosphocreatine goes through the novel high energy phosphate, phosphocreatinine, as an intermediate.

Animals↗
PubMed1984

Ca2+ can affect Vmax without changes in myosin light chain phosphorylation in smooth muscle.

The effects of elevated [Ca2+]o on crossbridge cycling rate, measured as maximum velocity of shortening (Vmax) and high energy phosphate usage (delta approximately P), and on the degree of phosphorylation of the 20,000-dalton light chain of myosin (MyLCP) during an isometric tetanus were determined in the rabbit taenia coli at 18 degrees C. In an normal Krebs medium (1.9 mM Ca2+) the average rate of delta approximately P during force development is 4 X higher than during force maintenance. In 4.5 mM Ca2+-Krebs, the average rate of delta approximately P increases by 100% during force development and during force maintenance above that observed in normal Krebs medium, with no significant change in force output. Vmax increased in the high Ca2+ medium, in good agreement with the corresponding rates of delta approximately P, but without any significant change in the degree of MyLCP. Also, in both high and low calcium media, Vmax decreased with tetanus duration as did the delta approximately P; however, the degree of phosphorylation was not directly related to the average rate of energy usage during the two phases of the tetanus. Therefore, in intact smooth muscles Ca2+-dependent and time-dependent changes in Vmax and average rate of delta approximately P can occur without corresponding changes in MyLCP. Modulation of crossbridge cycling rate may be accomplished by a Ca2+-dependent process in addition to MyLCP.

Animals↗
PubMed1984

Chemical energy usage during stimulation and stretch of mammalian smooth muscle.

High energy phosphate usage was measured in the rabbit taenia coli subjected to stimulation and stretch (0.12 Lo/min) and was compared to that observed previously under isometric conditions. When the muscle was bathed in a medium containing 1.9 mM Ca2+, stretch during the period of initial force development substantially decreased the rate of chemical energy usage compared to that under isometric conditions. When crossbridge cycling rate under isometric conditions was increased by incubation of the muscle in a medium containing 4.5 mM Ca2+, there was a greater decrease in rate of high energy phosphate usage during stretch compared to isometric conditions. The low energy usage during stretch occurs even though average active force output was approximately 40% higher than that under isometric conditions. During the period of subsequent force maintenance when both energy usage and crossbridge cycling rate under isometric conditions were low, there was no significant effect of stretch on the average rate of energy usage at either Ca2+ level. These results are consistent with the hypothesis that during stimulation and stretch in smooth muscle, crossbridge attachment and force production can occur even though the actin-activated myosin ATPase activity normally associated with isometric force development is greatly suppressed.

Animals↗
PubMed1984

Chemical energy usage and myosin light chain phosphorylation in mammalian skeletal muscle.

The purpose of this study was to ascertain whether phosphorylation of the regulatory light chain of myosin plays a role in modulating the rate of chemical energy usage in mammalian skeletal muscle. There was no change in the average rate of chemical energy usage with duration of isometric stimulation in the rat extensor digitorum longus (EDL), even though the degree of light chain phosphorylation increased from 5% at rest to above 60% after 7 s of stimulation. When the initial degree of phosphorylation was increased to 73% by prestimulation of the muscle, there was still no change in the chemical energy usage under isometric conditions. In contrast, under the conditions used, the mouse EDL showed changes in the average rate of energy usage that depended upon both tetanus duration and stimulation history. However, there was no consistent relationship between phosphorylation of the light chain and average rate of chemical energy usage. These results suggest that while there are factors which can change crossbridge cycling rate in mammalian skeletal muscle, phosphorylation of the regulatory light chain of myosin is neither necessary nor sufficient to cause such changes.

Animals↗
PubMed1983

Myosin light chain phosphorylation does not modulate cross-bridge cycling rate in mouse skeletal muscle.

An attempt was made to determine whether phosphorylation of the myosin light chain represents a thick filament-associated mechanism for modulating the rate of cross-bridge cycling in mouse skeletal muscle. When the degree of light chain phosphorylation was varied independently of tetanus duration, there was no correlation of phosphorylation with cross-bridge turnover rate, as measured by the shortening velocity of the muscle. It is concluded that in intact skeletal muscle phosphorylation of the myosin light chain does not in itself modulate cross-bridge cycling rate and that previously reported changes in cycling rate were due to other factors that may vary with tetanus duration.

Animals↗
PubMed1983

Chemical energy usage and myosin light chain phosphorylation in mammalian smooth muscle.

Experiments have been done to determine the relationships among active force output, average rate of high-energy phosphate utilization, and the degree of phosphorylation of the 20,000-dalton myosin light chain in the rabbit tenia coli at 18 C. During an isometric tetanus at l0 the degree of light chain phosphorylation increases to a maximum of 30-40% before maximum force is developed, and then phosphorylation slowly decreases while active force is maintained. During the period when there is a small decrease in degree of phosphorylation, the average rate of chemical energy usage falls by fourfold. In contrast, when the calcium concentration of the bathing medium is lowered from 1.9 to 1.0 mM a very large decrease in degree of phosphorylation is associated with only a small decrease in both energy usage and active force. At lower calcium levels both force and chemical energy usage decrease proportionately with little further decrease in degree of phosphorylation. We conclude that under isometric conditions there is no consistent relationship between degree of myosin light chain phosphorylation and the rate of cross-bridge cycling as measured by the rate of high-energy phosphate usage in this mammalian smooth muscle.

Adenosine Triphosphatases↗
PubMed1982

Chemical Energetics of contraction in mammalian smooth muscle.

Measurements of high-energy phosphate utilization during isometric tetanic contractions were made on a rabbit taenia coli preparation that had been treated so that respiration and glycolysis were blocked without altering the mechanical response to the muscle. At 18 C the first sign of high-energy phosphate usage after electrical stimulation was a net breakdown of ATP with a subsequent net resynthesis when the rate of phosphocreatine breakdown was high. The average rate of chemical energy usage was more than four times as high during the period of initial force development compared to that during maximum force maintenance. This initial high rate of energy usage was not due only to the internal work done against the series elasticity during force development. Comparison of energetics and mechanics data for the rabbit taenia coli and frog sartorius showed that smooth muscle was 100-fold more economical in maintaining isometric force and probably had a cross-bridge cycle time that was about 150-fold slower. The rate of energy usage during relaxation from an isometric tetanus in smooth muscle was very low, and force was exerted with a lower expenditure of energy during relaxation than during maximum force maintenance. Phosphorylation of the 20,000-dalton light chain of myosin occurred to the extent of 32% during a maximally activated isometric tetanus and was not proportional to the rate of energy usage during different stages of the tetanus. During isometric relaxation, the degree of phosphorylation, rate of energy usage, and active state all decreased more quickly than did active force output.

Adenosine Triphosphate↗
PubMed1980

Chemical energetics of force development, force maintenance, and relaxation in mammalian smooth muscle.

High-energy phosphate utilization (delta approximately P) associated with force development, force maintenance, and relaxation has been determined during single isometric tetani in the rabbit taenia coli. ATP resynthesis from glycolysis and respiration was stopped without deleterious effects on the muscle. At 18 degrees C and a muscle length of 95% l0, the resting rate of energy utilization is 1.8 +/- 0.2 nmol/g . s-1, or 0.85 +/- 0.2 mmol approximately P/mol of total creatine (Ct) . s-1, where Ct = 2.7 mumol/g wet wt. During the initial 25 s of stimulation when force is developed, the average rate of delta approximately P was -8.2 +/- 0.8 mmol/mol Ct . s-1, some four times greater than during the subsequent 35 s of force maintenance, when the rate was -2.0 +/- 0.6 mmol approximately P/mol Ct . s-1. The energy cost of force redevelopment (0 to 95% P0) after a quick release from the peak of a tetanus is very low compared with the initial force development. Therefore, the high rate of energy utilization during force development is not due only to internal work done against the series elasticity nor to any high rate of cross-bridge cycling inherently associated with force development. The high economy of force maintenance compared with other muscle types is undoubtedly due to a slower cross-bridge cycle time. The energy utilization during 45 s of relaxation was not statistically significant, and integral of Pdt/delta approximately P was higher during relaxation than during force maintenance in the stimulated muscle.

Adenosine Triphosphate↗
PubMed1978

Chemical energetics of single isometric tetani in mammalian smooth muscle.

A rabbit taenia coli preparation has been used to study the chemical energetics of smooth muscle contraction. Under the experimental conditions, the muscle had no spontaneous mechanical activity, but could be fully activated with the use of electrical field stimulation. ATP resynthesis from glycolysis and respiration was stopped with a procedure that involved treatment with metabolic inhibitors at 5 degrees C followed by rewarming to 18 degrees C. This procedure did not alter the high-energy phosphate contents of mechanical responses of the muscle. Use of this preparation to determine ATP and phosphorylcreatine changes during isometric tetani at 18 degrees C and a length of 86% LO showed that there was net ATP breakdown initially with no significant phosphorylcreatine splitting. This was followed by an increase in the rate of phosphorylcreatine splitting with net ATP synthesis. The average rate of total high-energy phosphate utilization was about 0.01 mumol/g.s for up to 60 s or about 150 times less than that of frog sartorius at the same temperature.

Adenosine Triphosphate↗