Cromakalim (BRL 34915) restores in vitro the membrane potential of depolarized human skeletal muscle fibres

The purpose of the present study was to analyze the effects of cromakalim (BRL 34915), a potent drug from a new class of drugs characterized as K+ channel openers, on the electrical activity of human skeletal muscle. Therefore, intracellular recordings were used to measure the effects of cromakalim on the membrane potential and input conductance of fibres from human skeletal muscle biopsies. Cromakalim in a concentration above 1 mol/l induced an increase in membrane K+ conductance. This effect resulted in a membrane hyperpolarization. The magnitude of this polarization depended on the difference between resting and K+ equilibrium potential. The effect had a rapid onset and was quickly reversible after washing. Fibres from two patients with hyperkalaemic periodic paralysis showed an excessive membrane depolarization during and also after exposure to an slightly elevated extracellular K+ concentration. In the latter situation, cromakalim repolarized the fibres to the normal resting potential. Tolbutamide (1 mmol/l) and Ba2+ (3 mmol/l) strongly antagonized the effect of cromakalim. The data show that cromakalim hyperpolarizes depolarized human skeletal muscle fibres maintained in vitro. The underlying mechanism is probably an activation of otherwise silent, ATP-regulated K+ channels. Such an effect may be of therapeutic benefit in a situation in which a membrane depolarization causes muscle paralysis

Taxation of Electronic Commerce

No other innovation, or way of doing business, has revolutionized the international economy faster than the Internet. It took generations for the Industrial Revolution to play out around the world while the Internet Revolution has unfolded in less than a decade. The speed of this change has been astounding. In the Industrial Age, as change took place, governments were able to react accordingly. In the Internet Age, today\u27s innovation is tomorrow\u27s standard. Government are finding that they must act on Internet time, which is a daunting challenge. This paper examines the current state of affairs with regards to the taxation of Internet commerce. It analysis the historical perspective of the United States of America, the OECD, the WTO, and the European Union; and attempts to answer the question “What happens next?” Is there an opportunity here for developing countries to increase their tax base

Exploring eternal stability with the simple harmonic universe

We construct nonsingular cyclic cosmologies that respect the null energy condition, have a large hierarchy between the minimum and maximum size of the universe, and are stable under linearized fluctuations. The models are supported by a combination of positive curvature, a negative cosmological constant, cosmic strings and matter that at the homogeneous level behaves as a perfect fluid with equation of state -1 < w < -1/3. We investigate analytically the stability of the perturbation equations and discuss the role of parametric resonances and nonlinear corrections. Finally, we argue that Casimir energy contributions associated to the compact spatial slices can become important at short scales and lift nonperturbative decays towards vanishing size. This class of models (particularly in the static limit) can then provide a useful framework for studying the question of the ultimate (meta)stability of an eternal universe.Comment: 22 pages, 2 figure