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L E Moore

Publications and source records attributed to L E Moore.

At least 73 records · Page 4Linked to original sources

Comparison of steady-state electrophysiological properties of isolated cells from bullfrog atrium and sinus venosus.

Single electrode whole cell voltage-clamp experiments and frequency domain analyses have been used to study and compare the K+ currents in enzymatically dispersed single cells from the atrium and the sinus venosus (pacemaker region) of the bullfrog heart. Admittance measurements made near the "resting' or zero-current potential yield data from which the equivalent circuit of each cell type may be obtained. Data from both atrial and pacemaker cells are well-fitted by a model consisting only of parallel resistance-capacitative elements, as predicted from their micro-anatomy. Neither of these amphibian cardiac cells contain a transverse tubule system (TT) and both have very little sarcoplasmic reticulum (SR). These results complement and extend two earlier investigations: (i) Moore, Schmid and Isenberg (J. Membrane Biol. 81:29-40, 1984) have reported that in guinea pig ventricle cells (which do contain an internal membrane system consisting of transverse tubules and a substantial SR) the SR may be electrically coupled to the sarcolemma; (ii) Shibata and Giles (Biophys. J. 45:136a, 1984) have shown that although bullfrog atrial cells have an inwardly rectifying background K+ current, IK1, pacemaker cells from the immediately adjacent sinus venosus do not. Data from admittance measurements also provide evidence that a TTX-insensitive inward Ca2+ current is activated in the pacemaker range of potentials.

Action Potentials↗

Rioprostil prevents gastric bleeding induced by nonsteroidal antiinflammatory drugs in dogs and arthritic rats.

Gastrointestinal irritation is the most significant side effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAID) for treatment of arthritic conditions. Rioprostil, a primary alcohol prostaglandin E1 analog, prevents gastric bleeding induced by several NSAID in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of rioprostil (50 micrograms/kg BID for 15 days) did not influence the course of the adjuvant disease in rats or alter the antiinflammatory or analgesic effect of the NSAID. In a 13 week efficacy study in dogs, rioprostil (40-60 micrograms/kg, PO) completely prevented gastric hemorrhagic lesions induced by daily administration of aspirin.

Animals↗

White noise analysis of cable properties of neuroblastoma cells and lamprey central neurons.

The integrative properties of two kinds of excitable cells, a cultured neuroblastoma cell and the lamprey giant interneuron, are described using a white-noise impedance method. The impedance functions were fitted with a neuron model consisting of an isopotential soma plus a single equivalent dendritic process, which contained up to 16 equal elements. The frequency-domain characteristics of both the passive and active conductances were used to estimate the dendritic-to-soma areas, the electrotonic length of an equivalent dendrite, the membrane time constant, and the relaxation time constants associated with the voltage-dependent conductances. The effect of differing degrees of synaptic input was simulated by localizing the synaptically activated conductances to the soma, a point at the end of the dendrite, or the entire dendritic membrane.

Animals↗

Linear electrical properties of isolated cardiac cells.

A frequency domain equivalent circuit analysis of isolated ventricular cells indicated the presence of an internal membrane structure which has a total capacitance four- to sixfold larger than the surface membrane. The internal membrane was mainly attributed to the sarcoplasmic reticulum since other morphological studies have shown that its area is many-fold larger than that of the surface membrane. Corresponding estimates from the transverse tubular system indicate an area less than that of the surface; thus this structure is not a likely candidate for the observed internal capacitance. Measurements in hypertonic solutions showed that the access resistance to the internal membrane reversibly increased as the tonicity was elevated. Freeze-fractured electron microscopic studies confirmed that hypertonic solutions increased the volume of transverse tubular system, which thus appears to have little relation to the access resistance. The most probable source of the access resistance is the diadic junction to the sarcoplasmic reticulum, which therefore would electrically couple it to the surface membrane.

Animals↗

Ion conductances of the surface and transverse tubular membranes of skeletal muscle.

A combination voltage clamp and admittance analysis of single skeletal muscle fibers showed that moderate depolarizations activated a steady-state negative sodium conductance in both the surface and transverse tubular membranes. The density of the voltage-dependent channels was similar for the surface and tubular conductances. The relaxation times associated with the negative conductance were in the millisecond range and markedly potential dependent. The negative tubular conductance has the consequence of increasing the apparent steady-state radial space constant to large values. This occurs because the positive conductance is counterbalanced by the maintained inward-going sodium current. The enhancement of the space constant by a negative conductance provides a means for the nearly simultaneous activation of excitation-contraction coupling.

Animals↗

Fluctuation and linear analysis of Na-current kinetics in squid axon.

The power spectrum of current fluctuations and the complex admittance of squid axon were determined in the frequency range 12.5 to 5,000 Hx during membrane voltage clamps to the same potentials in the same axon during internal perfusion with cesium. The complex admittance was determined rapidly and with high resolution by a fast Fourier transform computation of the current response, acquired after a steady state was attained, to a synthesized signal with predetermined spectral characteristics superposed as a continuous, repetitive, small perturbation on step voltage clamps. Linear conduction parameters were estimated directly from admittance data by fitting an admittance model, derived from the linearized Hodgkin-Huxley equations modified by replacing the membrane capacitance with a "constant-phase-angle" capacitance, to the data. The constant phase angle obtained was approximately 80 degrees. At depolarizations the phase of the admittance was 180 degrees, and the real part of the impedance locus was in the left-half complex plane for frequencies below 1 kHz, which indicates a steady-state negative Na conductance. The fits also yielded estimates of the natural frequencies of Na "activation" and "inactivation" processes. By fitting Na-current noise spectra with a double Lorentzian function, a lower and an upper corner frequency were obtained; these were compared with the two natural frequencies determined from admittance analysis at the corresponding potentials. The frequencies from fluctuation analyses ranged from 1.0 to 10.3 times higher than those from linear (admittance) analysis. This discrepancy is consistent with the concept that the fluctuations reflect a nonlinear rate process that cannot be fully characterized by linear perturbation analysis. Comparison of the real part of the admittance and the current noise spectrum shows that the Nyquist relation, which generally applies to equilibrium conductors, does not hold for the Na process in squid axon. The Na-channel conductance, gamma Na, was found to increase monotonically from 0.1 to 4.8 pS for depolarizations up to 50 mV from a holding potential of -60 mV, with no indication of a maximum value.

Animals↗

Small-signal analysis of K+ conduction in squid axons.

The maximum potential displacement that gives a linear K conductance response was determined to be 1 mV (rms) from a voltage-clamp analysis of TTX treated axons. For perturbations below this amplitude the K conductance kinetics are indistinguishable from a first-order rate process. Linearity and order of kinetics were assessed by four types of measurements: (i) the shape of the onset of the potassium current (sigmoidal vs. exponential); (ii) the symmetry of small hyperpolarizing and depolarizing pulses, (iii) wide band admittance, and (iv) harmonic analysis. The simplest interpretation of the results is that the small-signal linear response arises from a first-order gating mechanism, whereas the large-signal conventional voltage-clamp pulse of tens of millivolts evokes nonlinear phenomena. The small-signal results are consistent with the Hodgkin-Huxley description or any other nonlinear model which fits the large signal data and produces a linear first-order response for small perturbations.

Animals↗

Complex admittance of Na+ conduction in squid axon.

The complex admittance, Y(p), of squid axon was measured (4--1000 Hz) during step voltage clamp to obtain linear data on Na+ conduction. Y(p) is used as a spectroscopic tool to identify Na+ and K+ conduction, which dominate Y(p) at low frequencies and can be separated from each other and from the static capacitance. Na+ conduction is readily distinguishable from K+ conduction in that it produces a steady-state negative conductance. The admittance of the Na+ system can show an anomalous resonance or an antiresonance depending on whether the net shunt conductance is negative or positive. Use of the Na+ negative conductance to neutralize leakage yields a measurement of dielectric capacitance at low frequency. A 90 degrees phase angle suggests that the capacitance is ideal.

Animals↗

Chemically induced K+ conduction noise in squid axon.

Internal perfusion of tetraethylammonium ions (TEA) in squid axons produces a significant high frequency noise component. Although internal TEA suppresses the potassium conductance (GK) noise at relatively low frequencies, it induces high frequency noise which exceeds the intensity of the normal potassium and sodium noise. In addition, the induced noise is dependent on the presence of internal potassium ions (K+) suggesting that this source of noise arises from a modulation of the K+ conductance due to the blocking and unblocking of the K+ channel. The simplest model describing the TEA data is a two-step sequential, pseudo-unimolecular reaction where TEA binds during an open conductance state. A unit channel conductance of 2 pS is estimated from the TEA data as well as noise induced by triethyldecylammonium (TEDA) ions. Thus, these data are consistent with the hypothesis that the channel is blocked whenever the quaternary ammonium ion binding site, located near or within the K+ channel, is occupied.

Animals↗

K+ conduction description from the low frequency impedance and admittance of squid axon.

The form of power spectra of K+ conduction fluctuations in patches of squid axon suggested that K+ conduction kinetics are higher than first order (Fishman, Moore & Poussart, 1975, J. Membrane Biol. 24:305). To obtain an alternative description of ion conduction kinetics consistent with spontaneous fluctuations, the complex impedance and admittance of squid (Loligo pealei) axon were measured at low frequencies (1-1000 Hz) with a four electrode system using white Gaussian noise as a stochastic perturbation. As predicted from the spontaneous noise measurements, a low frequency impedance feature is observed between 1 and 30 Hz which is voltage and temperature dependent, disappears after substantial reduction in [Ki+], and is unaffected by the state of Na+ conduction or active transport. These measurements confirm and constitute strong support for the patch noise measurements and interpretations. The linearized Hodgkin-Huxley (HH) equations do not produce the low frequency feature since first order ion conduction kinetics are assumed. Computation of diffusion polarization effects associated with the axon sheath gives a qualitative account of the low frequency feature, but the potential dependence is opposite to that of the data. Thus, K+ conduction kinetics in the axon are not adequately described by a single first order process. In addition, significant changes in HH parameter values were required to describe the usual impedance (resonance) feature in Loligo pealei axon data.

Animals↗

Asymmetry currents and admittance in squid axons.

The complex admittance of squid (Loligo pealei) axon was measured rapidly (within 1 s) with pseudo-random small signals and discrete Fourier transform techniques under guarded, "space-clamp" conditions and during suppression of ion conduction. Asymmetry currents were measured by paired step clam pulses of +/-70 mV from a holding potential of -97 mV and gave an apparent capacitance of 0.36 muF/cm2. However, the admittance data showed no change in capacitance at holding potentials from -97 to -67 mV and gave a decrease of 0.07 of 0.15 muF/cm2 at -37 mV. The failure to observe a capacitance increase at low membrane potentials suggests the following possibilities: (a) the asymmetry current is a displacement current that inactivates completely with time, and (b) the asymmetry current is not a displacement current and arises from large signal effects (i.e., delayed nonlinearity in ionic current) on the membrane.

Animals↗

Fluctuation and relaxation analysis of monazomycin-induced conductance in black lipid membranes.

Fluctuation and relaxation analyses were performed on monazomycin-induced conductance of lipid bilayer membranes. With both methods a slow (sec) and a fast (msec) current component are apparent; however, the amplitude of the slow, voltage-dependent process is greater than that of the fast component in the step relaxation experiment and less in the fluctuation experiment. The fluctuation analysis showed principally a rapid voltage-dependent process which appears to be related to the multistate character of the conducting channel. The experimental results are interpreted in terms of a simplified kinetic model which is used to calculate relaxation and noise amplitudes.

Alamethicin↗

Noise measurements in squid axon membrane.

A small area (10(-4) to 10(-5) cm2 patch) of the external surface of a squid (Loligo pealei) axon was "isolated" electrically by means of a pair of concentric glass pipettes and sucrose solution to achieve a low extraneous noise measurement of spontaneous fluctuations in membrane potential and current. The measured "small-signal" impedance function of the isolated patch in seawater was constant at low frequencies and declined monotonically at frequencies beyond 100Hz. It is shown that the power-density spectrum (PDS) of voltage noise, which generally reflects the current-noise spectrum filtered by the membrane impedance function, is equivalent to the power spectrum of current-noise up to frequencies where the impedance decline is significant (Fishman, 1973a, Proc. Nat. Acad. Sci. USA 70:876). This result is in contrast to an impedance resonance measured under uniform constant-current (internal axial wire) conditions, for which the voltage-noise PDS reflects the impedance resonance. The overdamped resonance in the patch technique is a consequence of the relatively low resistance (1 Momega) pathways through the sucrose solution in the interstitial Schwann cell space which surround and shunt the high resistance (10-100 Momega) membrane patch. Current-noise measurements during patch voltage clamp extend observation of patch ion-conductance fluctuations to 1 kHz. Various tests are presented to demonstrate the temporal and spatial adequacey of patch potential control during current-noise measurements.

Animals↗