What can isolated skeletal muscle experiments tell us about the effects of caffeine on exercise performance?

Caffeine is an increasingly popular nutritional supplement due to the legal, significant improvements in sporting performance that it has been documented to elicit, with minimal side effects. Therefore, the effects of caffeine on human performance continue to be a popular area of research as we strive to improve our understanding of this drug and make more precise recommendations for its use in sport. Although variations in exercise intensity seems to affect its ergogenic benefits, it is largely thought that caffeine can induce significant improvements in endurance, power and strength-based activities. There are a number of limitations to testing caffeine-induced effects on human performance that can be better controlled when investigating its effects on isolated muscles under in vitro conditions. The hydrophobic nature of caffeine results in a post-digestion distribution to all tissues of the body making it difficult to accurately quantify its key mechanism of action. This review considers the contribution of evidence from isolated muscle studies to our understating of the direct effects of caffeine on muscle during human performance. The body of in vitro evidence presented suggests that caffeine can directly potentiate skeletal muscle force, work and power, which may be important contributors to the performance-enhancing effects seen in humans

A model for the transfer of conformational change in the phospholipid headgroup towards the hydrophobic interior of the membrane via a phosphorus(V) trigonal bipyramidal intermediate

Co-ordination change of phosphorus may be responsible for a decrease of the cross-sectional area of the phospholipid headgroup and a reduction of the difference in effective chain length between both acyl chains of a phospholipid molecule. Both factors induce a change in the angle of tilt of the acyl chains, leading to increasing or decreasing lateral phase separation

The influence of caffeine on intramembrane charge movements in intact frog striated muscle

The influence of caffeine, applied over a 25-fold range of concentrations, on intramembrane charge movements was examined in intact voltage-clamped amphibian muscle fibres studied in the hypertonic gluconate-containing solutions that were hitherto reported to emphasize the features of qγ at the expense of those of qβ charge.The total charge, Qmax, the transition voltage, V*, and the steepness factor, k, of the steady-state charge-voltage relationships, Q(V), were all conserved to values expected with significant contributions from the steeply voltage-dependent qγ species (Qmax ≈ 20 nC μF−1, V* ≈ −50 mV, k ≈ 8 mV) through all the applications of caffeine concentrations between 0.2 and 5.0 mm. This differs from recent reports from studies in cut as opposed to intact fibres.The delayed transients that have been attributed to transitions within the qγ charge persisted at low (0.2 mm) and intermediate (1.0 mm) caffeine concentrations.In contrast, the time courses of such qγ currents became more rapid and their waveforms consequently merged with the earlier qβ decays at higher (5.0 mm) reagent concentrations. The charging records became single monotonic decays from which individual contributions could not be distinguished. This suggests that caffeine modified the kinetic properties of the qγ system but preserved its steady-state properties. These findings thus differ from earlier reports that high caffeine concentrations enhanced the prominence of delayed transient components in cut fibres.Caffeine (5.0 mm) and ryanodine (0.1 mm) exerted antagonistic actions upon qγ charge movements. The addition of caffeine restored the delayed time courses that were lost in ryanodine-containing solutions, reversed the shift these produced in the steady-state charge-voltage relationship but preserved both the maximum charge, Qmax, and the steepness, k, of the steady-state Q(V) relationships.Caffeine also antagonized the actions of tetracaine on the total available qγ charge, but did so only at the low and not at the high applied concentrations. Thus, 0.2 mm caffeine restored the steady-state qγ charge, the steepness of the overall Q(V) function and the appearance of delayed qγ charge movements that had been previously abolished by the addition of 2.0 mm tetracaine.In contrast, the higher applied (1.0 and 5.0 mm) caffeine concentrations paradoxically did not modify these actions of tetracaine. The total charge and voltage dependence of the Q(V) curves, and the amplitude and time course of charge movements remained at the reduced values expected for the tetracaine-resistant qβ charge.These results permit a scheme in which caffeine acts directly upon ryanodine receptor (RyR)-Ca2+ release channels whose consequent activation then dissociates them from the tubular dihydropyridine receptor (DHPR) voltage sensors that produce qγ charge movement, with which they normally are coupled in reciprocal allosteric contact