What electrical measurements can say about changes in fault systems.

Earthquake zones in the upper crust are usually more conductive than the surrounding rocks, and electrical geophysical measurements can be used to map these zones. Magnetotelluric (MT) measurements across fault zones that are parallel to the coast and not too far away can also give some important information about the lower crustal zone. This is because the long-period electric currents coming from the ocean gradually leak into the mantle, but the lower crust is usually very resistive and very little leakage takes place. If a lower crustal zone is less resistive it will be a leakage zone, and this can be seen because the MT phase will change as the ocean currents leave the upper crust. The San Andreas Fault is parallel to the ocean boundary and close enough to have a lot of extra ocean currents crossing the zone. The Loma Prieta zone, after the earthquake, showed a lot of ocean electric current leakage, suggesting that the lower crust under the fault zone was much more conductive than normal. It is hard to believe that water, which is responsible for the conductivity, had time to get into the lower crustal zone, so it was probably always there, but not well connected. If this is true, then the poorly connected water would be at a pressure close to the rock pressure, and it may play a role in modifying the fluid pressure in the upper crust fault zone. We also have telluric measurements across the San Andreas Fault near Palmdale from 1979 to 1990, and beginning in 1985 we saw changes in the telluric signals on the fault zone and east of the fault zone compared with the signals west of the fault zone. These measurements were probably seeing a better connection of the lower crust fluids taking place, and this may result in a fluid flow from the lower crust to the upper crust. This could be a factor in changing the strength of the upper crust fault zone.

Neuronal coincidence detection by voltage-sensitive electrical synapses

Coincidence detection is important for functions as diverse as Hebbian learning, binaural localization, and visual attention. We show here that extremely precise coincidence detection is a natural consequence of the normal function of rectifying electrical synapses. Such synapses open to bidirectional current flow when presynaptic cells depolarize relative to their postsynaptic targets and remain open until well after completion of presynaptic spikes. When multiple input neurons fire simultaneously, the synaptic currents sum effectively and produce a large excitatory postsynaptic potential. However, when some inputs are delayed relative to the rest, their contributions are reduced because the early excitatory postsynaptic potential retards the opening of additional voltage-sensitive synapses, and the late synaptic currents are shunted by already opened junctions. These mechanisms account for the ability of the lateral giant neurons of crayfish to sum synchronous inputs, but not inputs separated by only 100 μsec. This coincidence detection enables crayfish to produce reflex escape responses only to very abrupt mechanical stimuli. In light of recent evidence that electrical synapses are common in the mammalian central nervous system, the mechanisms of coincidence detection described here may be widely used in many systems.

Visual stimuli induce waves of electrical activity in turtle cortex

The computations involved in the processing of a visual scene invariably involve the interactions among neurons throughout all of visual cortex. One hypothesis is that the timing of neuronal activity, as well as the amplitude of activity, provides a means to encode features of objects. The experimental data from studies on cat [Gray, C. M., Konig, P., Engel, A. K. & Singer, W. (1989) Nature (London) 338, 334–337] support a view in which only synchronous (no phase lags) activity carries information about the visual scene. In contrast, theoretical studies suggest, on the one hand, the utility of multiple phases within a population of neurons as a means to encode independent visual features and, on the other hand, the likely existence of timing differences solely on the basis of network dynamics. Here we use widefield imaging in conjunction with voltage-sensitive dyes to record electrical activity from the virtually intact, unanesthetized turtle brain. Our data consist of single-trial measurements. We analyze our data in the frequency domain to isolate coherent events that lie in different frequency bands. Low frequency oscillations (<5 Hz) are seen in both ongoing activity and activity induced by visual stimuli. These oscillations propagate parallel to the afferent input. Higher frequency activity, with spectral peaks near 10 and 20 Hz, is seen solely in response to stimulation. This activity consists of plane waves and spiral-like waves, as well as more complex patterns. The plane waves have an average phase gradient of ≈π/2 radians/mm and propagate orthogonally to the low frequency waves. Our results show that large-scale differences in neuronal timing are present and persistent during visual processing.

Membrane transport mechanisms probed by capacitance measurements with megahertz voltage clamp.

We have used capacitance measurements with a 1-microsecond voltage clamp technique to probe electrogenic ion-transporter interactions in giant excised membrane patches. The hydrophobic ion dipicrylamine was used to test model predictions for a simple charge-moving reaction. The voltage and frequency dependencies of the apparent dipicrylamine-induced capacitance, monitored by 1-mV sinusoidal perturbations, correspond to single charges moving across 76% of the membrane field at a rate of 9500 s-1 at 0 mV. For the cardiac Na,K pump, the combined presence of cytoplasmic ATP and sodium induces an increase of apparent membrane capacitance which requires the presence of extracellular sodium. The dependencies of capacitance changes on frequency, voltage, ATP, and sodium verify that phosphorylation enables a slow, 300- to 900-s-1, pump transition (the E1-E2 conformational change), which in turn enables fast, electrogenic, extracellular sodium binding reactions. For the GAT1 (gamma-aminobutyric acid,Na,Cl) cotransporter, expressed in Xenopus oocyte membrane, we find that chloride binding from the cytoplasmic side, and probably sodium binding from the extracellular side, results in a decrease of membrane capacitance monitored with 1- to 50-kHz perturbation frequencies. Evidently, ion binding by the GAT1 transporter suppresses an intrinsic fast charge movement which may originate from a mobility of charged residues of the transporter binding sites. The results demonstrate that fast capacitance measurements can provide new insight into electrogenic processes closely associated with ion binding by membrane transporters.

Stimulation of growth factor receptor signal transduction by activation of voltage-sensitive calcium channels.

To understand the mechanisms by which electrical activity may generate long-term responses in the nervous system, we examined how activation of voltage-sensitive calcium channels (VSCCs) can stimulate the Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Calcium influx through L-type VSCCs leads to tyrosine phosphorylation of the adaptor protein Shc and its association with the adaptor protein Grb2, which is bound to the guanine nucleotide exchange factor Sos1. In response to calcium influx, Shc, Grb2, and Sos1 inducibly associate with a 180-kDa tyrosine-phosphorylated protein, which was determined to be the epidermal growth factor receptor (EGFR). Calcium influx induces tyrosine phosphorylation of the EGFR to levels that can activate the MAPK signaling pathway. Thus, ion channel activation stimulates growth factor receptor signal transduction.

Electrical currents associated with nucleotide transport by the reconstituted mitochondrial ADP/ATP carrier.

The electrophoretic export of ATP against the import of ADP in mitochondria bridges the intra- versus extramitochondrial ATP potential gap. Here we report that the electrical nature of the ADP/ATP exchange by the mitochondrial ADP/ATP carrier (AAC) can be directly studied by measuring the electrical currents via capacitive coupling of AAC-containing vesicles on a planar lipid membrane. The currents were induced by the rapid liberation of ATP or ADP with UV flash photolysis from caged nucleotides. Six different transport modes of the AAC were studied: heteroexchange with either ADP or ATP inside the vesicles, initiated by photolysis of caged ATP or ADP; homoexchange with ADPex/ADPin or ATPex/ATPin; and caged ADP or ATP with unloaded vesicles. The heteroexchange produced the largest currents with the longest duration in line with the electrical charge difference ATP4- versus ADP3-. Surprisingly, also in the homoexchange and with unloaded vesicles, small currents were measured with shorter duration. In all three modes with caged ATP, a negative charge moved into the vesicles and with caged ADP it moved out of the vesicles. All currents were completely inhibited by a mixture of the inhibitors of the AAC, carboxyatractyloside and hongkrekate, which proves that the currents are exclusively due to AAC function. The observed charge movements in the heteroexchange system agree with the prediction from transport studies in mitochondria and reconstituted vesicles. The unexpected charge movements in the homoexchange or unloaded systems are interpreted to reveal transmembrane rearrangements of charged sites in the AAC when occupied with ADP or ATP. The results also indicate that not only ATP4- but also ADP3- contribute, albeit in opposite direction, to the electrical nature of the ADP/ATP exchange, which is at variance with former conclusions from biochemical transport studies. These measurements open up new avenues of studying the electrical interactions of ADP and ATP with the AAC.

Electrical and synaptic properties of embryonic luteinizing hormone-releasing hormone neurons in explant cultures.

Voltage- and ligand-activated channels in embryonic neurons containing luteinizing hormone-releasing hormone (LHRH) were studied by patch-pipette, whole-cell current and voltage clamp techniques. LHRH neurons were maintained in explant cultures derived from olfactory pit regions of embryonic mice. Cells were marked intracellularly with Lucifer yellow following recording. Sixty-two cells were unequivocally identified as LHRH neurons by Lucifer yellow and LHRH immunocytochemistry. The cultured LHRH neurons had resting potentials around -50 mV, exhibited spontaneous discharges generated by intrinsic and/or synaptic activities and contained a time-dependent inward rectifier (Iir). Voltage clamp analysis of ionic currents in the LHRH neuron soma revealed a tetrodotoxin-sensitive Na+ current (INa) and two major types of K+ currents, a transient current (IA), a delayed rectifier current (IK) and low- and high-voltage-activated Ca2+ currents. Spontaneous depolarizing synaptic potentials and depolarizations induced by direct application of gamma-aminobutyrate were both inhibited by picrotoxin or bicuculline, demonstrating the presence of functional gamma-aminobutyrate type A synapses on these neurons. Responses to glutamate were found in LHRH neurons in older cultures. Thus, embryonic LHRH neurons not yet positioned in their postnatal environment in the forebrain contained a highly differentiated repertoire of voltage- and ligand-gated channels.