Showing papers in "Progress in Biophysics & Molecular Biology in 1973"

Excitation-contraction coupling in heart muscle: Membrane control of development of tension

Abstract: III. EXCITATION-CONTRACT/ON COUPLING PROCESSES IN THE MAMMALIAN VENTRICLE A. Structure 1. Transverse-tubular system 2. Sarcoplasmic reticulum B. Functional Implications of the Structure of the Mammalian Myocardium C. Action Potential Control of Contraction D. Membrane Potential and Development of Tension in Mammalian Ventricle E. Potassium Chloride Contracture Studies F. Ionic and Drug Dependence of the Two Components of Tension in Mammalian Heart 1. The phasic response 2. The tonic response G. The Mechanism of Development of the Tonic Tension H. The Mechanism of the Triggered Release of the Phasic Store 1. Secondary inward current and activation of contraction 2. Other observations concerning the secondary inward current I. Replenishment of the Phasic Store 1. Depletion of the activator store 2. Beat-dependent kinetics 3. Quantity of activator in the phasic store and the concept of recirculation 4. An estimate of the magnitude of the recirculated fraction of activator 5. Delay in availability of activator 6. Anatomical correlates 7, Plateau and replenishment J. A Model of the E.-C Coupling Mechanism in Mammalian Heart Muscle K. Events Leading to a Normal Contraction L. A Mechanism for the Altered Inotropic State (the Interval Strength Relation) 1. Post-extrasystolic potentiation 2. Treppe 3. Other theories (a) Inotropic mediator hypothesis (b) Sodium-lag hypothesis

Energetic aspects of nerve conduction: The relationships between heat production, electrical activity and metabolism

Abstract: Because of their small diameter, mammalian non-myelinated fibres have a much larger amount of nerve membrane per gram of tissue than do myelinated fibres or giant invertebrate axons. This has made them particularly suitable for the study of the energetic aspects of conduction. In these fibres at about 5°C, a single impulse is associated with the evolution of a positive heat of 24.5 μcal/g followed by a reabsorption of 22.2 μcal/g. These two phases of initial heat production leave a residual heat of about 2.3 μcal/g. Most, if not all, of the initial heat production can be accounted for by the physicochemical consequences of discharging and subsequently recharging the membrane capacity during the action potential. Part of the initial positive heat production is due to the free energy changes that accompany the discharging of the capacity; but most seems due to a large decrease in entropy in the dielectric on removal of the electric field across it. The observed changes in birefringence of the nerve on stimulation may agree with this interpretation. No evidence has been produced so far for a thermal manifestation of any chemical mechanism, such as hydrolysis of acetylcholine, controlling the permeability changes of the sites or channels through which the ions move during the spike. Such sites, indeed, seem to form such a small fraction of the nerve membrane that thermal and optical experiments, which are near the experimental limit of resolution at the moment, are unlikely to yield any information about them. The initial events are followed by a recovery period during which (following stimulation at 2.5 impulses per sec at 20°C) a total recovery heat of 93 μcal/g. impulse is produced. The corresponding extra oxygen consumed, 600–900 pmoles/g. impulse has a calorific equivalent that agrees well with this value. During this recovery period an increased utilization of ATP can be detected, resulting in an increase in the concentration of ADP. The increase in ADP concentration in turn causes a decrease in the concentration of NADH as it is oxidized to resynthesize the ADP to ATP; and this decrease in the concentration of the NADH can be monitored by following the native fluorescence of the nerve. The overall conclusion from these and other types of experiments is that ATP is the immediate fuel for the sodium pump. After depletion during impulse conduction, the ATP is resynthesized by electron transport, and oxidative phosphorylation. This is associated with aerobic glycolysis, glucose and glycogen being the crude sources of energy although substrates lower down the metabolic pathway such as pyruvate and acetate, and fructose, can also support pumping. There are thus a variety of methods by which the kinetics of pumping activity can be examined, all of which agree remarkably well with one another and any one of them in principle accurately reflects botht the magnitude and time course of pumping. The most convenient method at the moment for studying the metabolic response to impulse conduction in nerve seems to be the electrical method of following the electrogenically produced post-tetanic hyperpolarization.