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R M Simmons

Publications and source records attributed to R M Simmons.

At least 73 records · Page 4Linked to original sources
PubMed1978

Reaction mechanism of the magnesium ion-dependent adenosine triphosphatase of frog muscle myosin and subfragment 1.

The Mg2+-dependent ATPase (adenosine 5'-triphosphatase) mechanism of myosin and subfragment 1 prepared from frog leg muscle was investigated by transient kinetic technique. The results show that in general terms the mechanism is similar to that of the rabbit skeletal-muscle myosin ATPase. During subfragment-1 ATPase activity at 0-5 degrees C pH 7.0 and I0.15, the predominant component of the steady-state intermediate is a subfragment-1-products complex (E.ADP.Pi). Binary subfragment-1-ATP (E.ATP) and subfragment-1-ADP (E.ADP) complexes are the other main components of the steady-state intermediate, the relative concentrations of the three components E.ATP, E.ADP.Pi and E.ADP being 5.5:92.5:2.0 respectively. The frog myosin ATPase mechanism is distinguished from that of the rabbit at 0-5 degrees C by the low steady-state concentrations of E.ATP and E.ADP relative to that of E.ADP.Pi and can be described by: E + ATP k' + 1 in equilibrium k' - 1 E.ATP k' + 2 in equilibrium k' - 2 E.ADP.Pi k' + 3 in equilibrium k' - 3 E.ADP + Pi k' + 4 in equilibrium k' - 4 E + ADP. In the above conditions successive forward rate constants have values: k' + 1, 1.1 X 10(5)M-1.S-1; k' + 2 greater than 5s-1; k' + 3, 0.011 s-1; k' + 4, 0.5 s-1; k'-1 is probably less than 0.006s-1. The observed second-order rate constants of the association of actin to subfragment 1 and of ATP-induced dissociation of the actin-subfragment-1 complex are 5.5 X 10(4) M-1.S-1 and 7.4 X 10(5) M-1.S-1 respectively at 2-5 degrees C and pH 7.0. The physiological implications of these results are discussed.

Actins↗
PubMed1977

Tension responses to sudden length change in stimulated frog muscle fibres near slack length.

1. Apparatus for applying a step change of length to an isolated muscle fibre is described. The step was complete in about 0.2 ms.2. Effects of tendon compliance were eliminated by using a spot-follower device and by gripping the tendons with metal clips close to the fibre ends.3. The natural frequency of the force transducer was above 10 kHz.4. Steps of various amplitudes and in either direction were applied to isolated muscle fibres about 6 mm long from the anterior tibial muscle of Rana temporaria during tetanic stimulation. Initial sarcomere length was 2.0-2.2 mum, and temperature was 0-3 degrees C.5. The tension response to a step could be divided into four phases. The initial response was an apparently elastic change during the step itself (phase 1). After the step was completed there was a rapid partial recovery towards the original tension (phase 2, lasting 2-5 ms), followed by a slowing or reversal of recovery (phase 3, 10-50 ms), and finally a much slower return to the original tension (phase 4). Most of this paper is concerned with phases 1 and 2.6. The initial tension change (phase 1) occurred synchronously with the applied length change, indicating that the fibres possess a compliance which is almost linear and almost undamped. Its stiffness is such that an instantaneous shortening of about 4 nm per half-sarcomere would bring the tension to zero from its isometric value.7. The absence of detectable damping during phase 1 indicates that the viscosity of a stimulated fibre is substantially less than the apparent viscosity of a fibre at rest.8. The instantaneous force-extension curve approached the length axis at a sharp angle and a negative tension appeared at the force transducer when a very large step was applied. These observations suggest that the structures responsible for the stiffness of the fibre remain rigid when they are not under tension.9. During the few milliseconds after the step (phase 2) the tension recovered part of the way toward the level which existed before the step. In shortening steps the time course of this recovery was adequately fitted by the sum of four exponential terms, and was similar in steps of different amplitude but with a time scale shorter the larger the step. In stretches the slow components were relatively larger than in releases.10. The tension level, T(2), approached during phase 2 depended only on the total amplitude of the step and not on the time course of the length change, provided it was complete in 1-2 ms. The extreme tension reached during a step could thus vary widely without detectable change in T(2).11. With stretches and releases of up to about 3 nm per half-sarcomere this early recovery was almost complete, so that the curve of T(2) against step amplitude was nearly horizontal. With larger releases the line curved downwards, reaching zero in a release of about 14 nm per half-sarcomere.12. When the temperature was raised both the developed tension and the stiffness increased, but the relative increase was greater for tension than for stiffness. The amount of instantaneous shortening needed to bring tension to zero was therefore also increased.13. A set of empirical equations is given which describe adequately the first few milliseconds of the tension change in response to any imposed time course of shortening.14. The rapid elasticity and early tension recovery resemble the response of a combination of two elastic components and one viscous component. Reasons are given for preferring an interpretation in terms of an undamped compliance in series with a damped compliance (Voigt element) rather than an undamped elasticity in parallel with a series combination of viscous and elastic components (Maxwell element).15. The rapid compliance does not correspond to the ;series elastic component' of two-component theories of muscle contraction.

Animals↗
PubMed1976

Free energy levels and entropy production associated with biochemical kinetic diagrams.

"Basic" and "gross" free energy levels are defined for the discrete states of a macromolecular biochemical kinetic system such as a free energy transducing enzyme (e.g., myosin or Na,K-ATPase). Basic free energy level differences are related to the first-order rate constants for transitions between states while gross free energy differences, along with the corresponding fluxes, determine the rate of entropy production in the system. In muscle contraction the analysis is complicated by the possibility of the system doing external mechanical work. The question of the sign of the flux or of the gross free energy level change in a given transition is examined for both single-cycle and multi-cycle models. More definite statements can be made in single-cycle cases. Some numerical examples are included. The more complicated cases are reserved for a subsequent paper.

Adenosine Triphosphatases↗
PubMed1976

Free energy levels and entropy production in muscle contraction and in related solution systems.

"Basic" and "gross" free energy levels of a macromolecule such as myosin or Na,K-ATPase, defined in a previous publication, are discussed here for two relatively complicated cases: a six-state kinetic diagram of the sort that could be used to describe the actin activation of myosin-ATPase in solution; and muscle contraction, where a similar kinetic diagram is needed for each value of a positional variable X.

Actins↗
PubMed1976

The diencephalon of the vervet monkey (Cercopithecus aethiops). Part I: thalamus and metathalamus.

The diencephalon of the vervet monkey (Cercopithecus aethiops) is described and compared with that of other primates, particularly the macaque monkey (Macaca mulatta). In the vervet monkey, the thalamus is divided into six nuclear groups: anterior, midline, medial, dorsolateral, ventrolateral and posterior. The anterior nuclear group shows a regressive nucleus anterodorsalis and a poorly defined demarcation between the nuclei anteromedialis and anteroventralis. There is a large interthalamic adhesion in which the ventral region containing nuclei centralis medialis, interventralis and reuniens, shows more regression than the dorsal region consisting of nuclei parataenialis and paraventralis. As the nucleus medialis ventralis is not present, the nucleus medialis dorsalis is described as the nucleus medialis; this is clearly differentiated into three parts, each part showing different cytological and architectonic features. The nucleus centrum medianum is larger and better developed than that of lower primates but is not entirely demarcated from the nucleus parafascicularis. The pulvinar is an enormous outgrowth from the dorsolateral thalamic nuclei. The ventrolateral thalamic nuclei are well differentiated from one another: a distinct nucleus ventralis dorsomedialis is present and appears to possess definite topographical and cytological differences from those of the other ventrolateral nuclei. The nucleus ventralis posteromedialis is further differentiated into a magno- and a parvocellular part. The nucleus ventralis posteroinferioris is a distinct entity. The lateral geniculate body shows a definite differentiation into two nuclei: pregeniculate and lateral geniculate nuclei. The lateral geniculate nucleus is a six-layered structure which is of the inverted type; it has undergone a lateral rotation through an anteroposterior axis from a dorsal position in the prosimian thalamus to its present ventral position in the higher primate thalamus. The medial geniculate body is not laminated as is the lateral geniculate nucleus; it consists of a small dorsomedial magnocellular and a large ventrolateral parvocellular part.

Animals↗
PubMed1976

The diencephalon of the vervet monkey (Cercopithecus aethiops). Part II: epithalamus, subthalamus and hypothalamus.

The nuclear configuration and topography of the epithalamus, subthalamus and hypothalamus of the vervet monkey (Cercopithecus aethiops) are described and compared with those of other primates, particularly the macaque monkey. The epithalamus does not show any striking structural differences, except some architectonic differentiation in the lateral habenular nucleus. The subthalamus is a phylogenetically stable structure throughout the primate scale; it does not show any significant changes, except that it extends less rostrally and that the nuclei entopeduncularis and peripeduncularis are much smaller and less well defined in the vervet monkey than those in the diencephalon of lower primates. The nucleus subthalamicus and the fields of Forel, though small in size, are comparatively well developed; the zona incerta appears to be differentiated cytoarchitectonically into two parts. The hypothalamus is divided morphologically into four regions--the preoptic, supraoptic, infundibular and mamillary regions. Although the hypothalamus of the vervet monkey is topographically identifiable with those of other primates, there are cyto- and myeloarchitectonic differences to be found in certain hypothalamic nuclei and areas. The preoptic region is small and poorly delimited from the parolfactory region antierorly and the supraoptic region posteriorly. The nucleus paraventricularis is large and well differentiated into secretory and non-secretory portions; the nucleus supraopticus does not show cellular separation into dorsolateral and ventromedial parts as clearly as they are in other primates. The nucleus dorsomedialis is not as well defined as the nucleus ventromedialis like it is in other primates. The nucleus tuberalis lateralis is comparably small, and is not split into several cellular groups as it is in higher primates. The posterior hypothalamic area is morphologically the best definable of the hypothalamic areas. The mamillary region is developmentally advanced, and very well differentiated into medial, lateral and intercalated nuclei.

Animals↗