Author
A. Weber
Bio: A. Weber is an academic researcher from Saint Louis University. The author has contributed to research in topics: Calcium ATPase & ATP hydrolysis. The author has an hindex of 5, co-authored 5 publications receiving 1212 citations.
Papers
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TL;DR: A drop in temperature increased the caffeine-induced Ca release while procaine inhibited it and inhibited the rate of Ca uptake, which may in part account for the prolongation of the active state caused by caffeine.
Abstract: At concentrations between 1 to 10 mM, caffeine reduced the Ca-accumulating capacity of fragmented reticulum obtained from frog and rabbit muscle. With 8 mM caffeine enough Ca was released from frog reticulum to account for the force of the contracture. Caffeine did not affect all reticulum membranes equally. The fraction which was spun down at 2000 g was more sensitive than the lighter fractions. The percentage of the total accumulated Ca released by caffeine decreased with decreasing Ca content of the reticulum. In parallel with their known effects on the caffeine contracture, a drop in temperature increased the caffeine-induced Ca release while procaine inhibited it. Caffeine also inhibited the rate of Ca uptake, which may in part account for the prolongation of the active state caused by caffeine.
654 citations
TL;DR: Evidence is presented that caffeine does not act on the mitochondrial Ca uptake system and that its effect cannot be attributed to the accumulation of adenosine 3',5'-phosphate.
Abstract: Evidence is presented that caffeine does not act on the mitochondrial Ca uptake system and that its effect cannot be attributed to the accumulation of adenosine 3',5'-phosphate. Two distinct caffeine effects are described. At high ATP concentrations caffeine decreases the coupling between ATP hydrolysis and Ca inflow. It either inhibits inflow without any inhibition of the rate of ATP hydrolysis, or it stimulates the ATPase activity without stimulating Ca inflow. These high ATP concentrations (much higher than needed for the saturation of the transport ATPase) greatly reduce the control of the turnover rate of the transport system, by accumulated Ca. At low ATP concentrations when the transport system is under maximal control by accumulated Ca, caffeine inhibits the ATPase activity without affecting the rate of Ca inflow.
309 citations
TL;DR: The rate of ATP hydrolysis decreases very rapidly during the first 2 sec of calcium uptake, and changes with time in a manner similar to that described for calcium net uptake by other workers, suggesting that the two activities are coupled.
Abstract: The rate of ATP hydrolysis decreases very rapidly during the first 2 sec of calcium uptake. It changes with time in a manner similar to that described for calcium net uptake by other workers, suggesting that the two activities are coupled. The decline in both rates may be ascribed to an inhibitory effect of accumulated calcium on calcium influx and ATPase activity for the following reasons. During the steady state, Ca-Ca and Sr-Ca exchange and the rate of ATP hydrolysis are much slower than the initial rate of net calcium uptake and the associated ATP hydrolysis. If the accumulation of free calcium is prevented by calcium-oxalate precipitation the initial rate of net calcium uptake does not decay during prolonged periods of transport. Furthermore, passive preloading of vesicles with calcium inhibits the rate of hydrolysis in proportion to the extent of preloading. The inhibition of steady-state flux is alleviated by free ATP; i.e., not chelated with magnesium, but not by free ITP.
136 citations
TL;DR: These experiments do not support the view that relaxation is caused by the binding of NTP to a special inhibitory site but are quite compatible with the idea that relaxation depends on the extent to which the hydrolytic site is saturated with NTP.
Abstract: The Mg chelates of ITP, GTP, and UTP in addition to that of ATP were shown to be capable of causing complete relaxation of myofibrils as indicated by the complete inhibition of syneresis and the reduction of the NTPase activity to that of isolated myosin. For ITP and GTP the required concentrations were about 100 times higher than those for ATP, whereas UTP was maximally effective also in low concentrations (0.2 mM). For all NTP's the concentrations for relaxation were related to those necessary for contraction so that NTP concentrations which gave 80–90% maximal NTPase activity in the presence of Ca caused complete relaxation in the absence of Ca. Thus, these experiments do not support the view that relaxation is caused by the binding of NTP to a special inhibitory site but are quite compatible with the idea that relaxation depends on the extent to which the hydrolytic site is saturated with NTP. The Ca concentration required for contraction depends on the nature of the NTP base and its concentration; it is lower for ITP than for ATP and decreases with decreasing concentrations of ITP.
58 citations
TL;DR: The rate of ATP hydrolysis decreases very rapidly during the first 2 sec of calcium uptake, and changes with time in a manner similar to that described for calcium net uptake by other workers, suggesting that the two activities are coupled.
Abstract: The outflux of calcium from vesicles of sarcoplasmic reticulum is controlled by the concentration of ionized calcium in the medium. In a calcium-free medium calcium outflux is at a minimum provided ATP and Mg are present. If they are removed calcium outflux becomes rapid and has a rate constant similar to that of outflux during steady-state 40Ca-45Ca exchange with saturating calcium concentrations in the medium. In order to maintain the low permeability state of the membrane only the presence but not the continued hydrolysis of ATP is necessary.
58 citations
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TL;DR: The inhibitors of Ca-induced Ca release––procaine and adenine––were shown not to inhibit contraction of living skeletal muscle fibers induced by the depolarization of the surface membrane.
Abstract: Publisher Summary Ca release from the sarcoplasmic reticulum (SR) is one of the most important steps in excitation–contraction coupling of skeletal muscle. This chapter describes the physiological release of Ca from the SR, various modes of Ca release from the SR, and the physiological significance of various Ca release mechanisms. Ca ion is the mediator of information of action potentials to the contractile machinery; however, the physiological source of the mediator Ca is not yet unequivocally established. The inhibitors of Ca-induced Ca release––procaine and adenine––were shown not to inhibit contraction of living skeletal muscle fibers induced by the depolarization of the surface membrane. Studies of the ionic composition of the lumen of the SR by electron-probe analysis show that there are no significant differences between the ionic compositions in the lumen of the SR and that in the cytoplasm except for Ca ion. The essential part of the physiological Ca release mechanism is almost entirely unknown; therefore, further studies, especially by using preparations, such as improved cut fibers, that retain the physiological tubule (T)–SR coupling mechanism, but have easy access to sarcoplasm so that its composition can be altered at will, are necessary.
1,481 citations
TL;DR: Caffeine is the most widely consumed central-nervous-system stimulant as discussed by the authors, however, its psychostimulant action on man is often subtle and not very easy to detect.
1,320 citations
01 Jan 1974
TL;DR: The CRC Critical Reviews in Biochemistry: Vol. 2, No. 1, No. 1, pp. 1-65 as mentioned in this paper, reviewed Actin And Myosin And Cell Movemen.
Abstract: (1974). Actin And Myosin And Cell Movemen. CRC Critical Reviews in Biochemistry: Vol. 2, No. 1, pp. 1-65.
872 citations
TL;DR: Experiments done in skinned cardiac cells show that CICR is not all or none, and calculations of the Ca2+ buffering in the mammalian ventricular cell and of the systolic transsarcolemmal Ca 2+ influx do not support the alternative hypothesis that this influx of Ca2+, is large enough to activate the myofilaments directly.
760 citations
TL;DR: The repeated contractions which can be observed in skinned fibres in appropriate concentrations of caffeine, Ca2+ and chelating agent suggest that calcium release is a regenerative process in which calcium itself causes the release of calcium from the reticulum.
Abstract: The repeated contractions which can be observed in skinned fibres in appropriate concentrations of caffeine, Ca2+ and chelating agent suggest that calcium release is a regenerative process in which calcium itself causes the release of calcium from the reticulum.
751 citations