Magnesium induces neuronal apoptosis by suppressing excitability

In clinical obstetrics, magnesium sulfate (MgSO4) use is widespread, but effects on brain development are unknown. Many agents that depress neuronal excitability increase developmental neuroapoptosis. In this study, we used dissociated cultures of rodent hippocampus to examine the effects of Mg++ on excitability and survival. Mg++-induced caspase-3-associated cell loss at clinically relevant concentrations. Whole-cell patch-clamp techniques measured Mg++ effects on action potential threshold, action potential peak amplitude, spike number and changes in resting membrane potential. Mg++ depolarized action potential threshold, presumably from surface charge screening effects on voltage-gated sodium channels. Mg++ also decreased the number of action potentials in response to fixed current injection without affecting action potential peak amplitude. Surprisingly, Mg++ also depolarized neuronal resting potential in a concentration-dependent manner with a +5.2 mV shift at 10 mM. Voltage ramps suggested that Mg++ blocked a potassium conductance contributing to the resting potential. In spite of this depolarizing effect of Mg++, the net inhibitory effect of Mg++ nearly completely silenced neuronal network activity measured with multielectrode array recordings. We conclude that although Mg++ has complex effects on cellular excitability, the overall inhibitory influence of Mg++ decreases neuronal survival. Taken together with recent in vivo evidence, our results suggest that caution may be warranted in the use of Mg++ in clinical obstetrics and neonatology

Consequences of converting graded to action potentials upon neural information coding and energy efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ~50% in generator potentials, to ~3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation

Role of calcium and vesicle-docking proteins in remobilising dormant neuromuscular junctions in desert frogs

Despite prolonged immobility the desert frog, Cyclorana alboguttata, suffers little impairment in muscle function. To determine compensatory mechanisms at neuromuscular junctions, transmitter release was examined along primary terminals in C. alboguttata iliofibularis muscle. Using extracellular recording we found the amplitudes of evoked endplate currents were significantly smaller in dormant frogs. In active frogs we identified two negatively sloping proximal–distal gradients of transmitter frequency and quantal content; a shallow proximal–distal gradient with low probability of transmitter release (0.6). During aestivation, only a shallow gradient was identified. The high probability release sites in control frogs were inhibited during aestivation by a mechanism that could be reversed by (1) increasing the extracellular calcium concentration, and (2) increasing the frequency of stimulation. This suggests that transmitter vesicles are available during aestivation but not released. We quantified expression of messenger RNA transcripts coding for the transmitter vesicle-docking proteins synaptotagmin 1, syntaxin 1B and UNC-13. All three were rare transcripts maintained at control values during aestivation. Neuromuscular remobilisation after dormancy in C. alboguttata is more likely a product of rapidly reversible physiologic mechanisms than reorganisations of the neuromuscular transcriptome