Electron acceleration by wave turbulence in a magnetized plasma

Astrophysical shocks are commonly revealed by the non-thermal emission of energetic electrons accelerated in situ 1-3 . Strong shocks are expected to accelerate particles to very high energies 4-6 ; however, they require a source of particles with velocities fast enough to permit multiple shock crossings. While the resulting diffusive shock acceleration 4 process can account for observations, the kinetic physics regulating the continuous injection of non-thermal particles is not well understood. Indeed, this injection problem is particularly acute for electrons, which rely on high-frequency plasma fluctuations to raise them above the thermal pool 7,8 . Here we show, using laboratory laser-produced shock experiments, that, in the presence of a strong magnetic field, significant electron pre-heating is achieved. We demonstrate that the key mechanism in producing these energetic electrons is through the generation of lower-hybrid turbulence via shock-reflected ions. Our experimental results are analogous to many astrophysical systems, including the interaction of a comet with the solar wind 9 , a setting where electron acceleration via lower-hybrid waves is possible

Cardiac chloride channels: physiology, pharmacology and approaches for identifying novel modulators of activity.

Drugs that block cardiac cation channels have been marketed as the therapeutic answer to cardiac arrhythmia. However, such molecules have been only moderately successful at improving the survival of cardiac patients, and so new targets have been needed for future antiarrhythmic agents. This article outlines the properties and roles of Cl(-) channels, which are one of these new targets, and describes an approach for identifying novel CI(2) channel modulators

Polymyxin B has multiple blocking actions on the ATP-sensitive potassium channel in insulin-secreting cells

The action of polymyxin B (0.1 μM) on ATP-sensitive K+ (K+ ATP) channels in RINm5F insulin-secreting cells was investigated by patch-clamp techniques. Using inside-out patches, open-cells and outside-out patches, polymyxin B was found to block K+ ATP channels by, on average, approximately 90-95 of the initial control level of channel activity. The effects were rapid in onset, sustained and readily reversible. Similar effects were found in patches excised from cells pretreated overnight with 1 μM of the phorbol ester phorbol myristate acetate (PMA). External block of channels was associated with a marked decrease in single-channel current amplitude, whereas these effects were not seen when polymyxin B was added to the inside face of the membrane. In patches bathed with internally applied ATP (0.5 mM) and ADP (0.5 mM), polymyxin B inhibited channels but its actions were not reversible upon removal of the compound. However, when the same protocol was undertaken upon cells pre-treated with PMA, the effects of polymyxin B were readily reversed. Our data suggests that polymyxin B is a novel modulator of K+ ATP channels, exhibiting multiple blocking actions that may possibly involve a direct effect upon the channel and indirect effects mediated through the inhibition of endogenous protein kinase(s). © 1994 Springer-Verlag

AMPK modulates glucose-sensing in insulin-secreting cells by altered phosphotransfer to KATP channels

Glucose-sensing (GS) behaviour in pancreatic β-cells is dependent on ATP-sensitive K(+) channel (KATP) activity, which is controlled by the relative levels of the KATP ligands ATP and ADP, responsible for closing and opening KATP, respectively. However, the mechanism by which β-cells transfer energy status from mitochondria to KATP, and hence to altered electrical excitability and insulin secretion, is presently unclear. Recent work has demonstrated a critical role for AMP-activated protein kinase (AMPK) in GS behaviour of cells. Electrophysiological recordings, coupled with measurements of gene and protein expression were made from rat insulinoma cells to investigate whether AMPK activity regulates this energy transfer process. Using the whole-cell recording configuration with sufficient intracellular ATP to keep KATP closed, raised AMPK activity induced GS electrical behaviour. This effect was prevented by the AMPK inhibitor, compound C and required a phosphotransfer process. Indeed, high levels of intracellular phosphocreatine or the presence of the adenylate kinase (AK) inhibitor AP5A blocked this action of AMPK. Using conditions that maximised AMPK-induced KATP opening, there was a significant increase in AK1, AK2 and UCP2 mRNA expression. Thus we propose that KATP opening in response to lowered glucose concentration requires AMPK activity, perhaps in concert with increased AK and UCP2 to enable mitochondrial-derived ADP signals to be transferred to plasma membrane KATP by phosphotransfer cascades