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M Tarr

Publications and source records attributed to M Tarr.

At least 19 recordsLinked to original sources
PubMed2001

Photosensitization-induced calcium overload in cardiac cells: direct link to membrane permeabilization and calcium influx.

The purpose of the present study was to gain new insight regarding the role membrane permeabilization plays in the photosensitization-induced increase in intracellular calcium concentration. During continuous rose bengal photosensitization we monitored the contractile state (relaxed or hypercontracted) of isolated frog cardiac cells and assessed the photosensitization-induced membrane-leak conductance. We investigated the effects of irradiance, extracellular calcium concentration, intracellular chelation of calcium and substitution of tetraethylammonium (TEA) for extracellular sodium. We found that with 2 and 5 mM extracellular calcium cell hypercontracture occurred when leak conductance reached values on the order of 6-7 nS, independent of the illumination duration required to reach this conductance. With 0.5 mM calcium hypercontracture occurred when leak conductance reached values on the order of 11 nS. Chelation of intracellular calcium delayed the onset of cell hypercontracture and increased by two- to three-fold the leak conductance at the initiation of cell hypercontracture. Substitution of TEA for extracellular sodium did not affect the time to contracture onset but reduced leak conductance at contracture onset nearly three-fold. We discuss how our results support the conclusion that photosensitization induces an increase in intracellular calcium concentration via calcium influx through the transmembrane-permeability pathway opened by the photosensitization process.

Animals↗
PubMed2000

[Alteration of nitric oxide production during arterial myocardial revascularization using extracorporeal circulation. Quantitative measurement of EDNO production by the internal mammary artery bypass graft].

Authors measured the concentration of stable metabolite (NO2: nitrite) of EDNO (endothelium derived nitric oxide) in the internal mammary artery (IMA) bypass graft with the help of a previously reported method (measurement of effective blood flow capacity of the IMA graft in the coronary sinus). Nitrite level in the systemic circulation prior to extracorporeal circulation (ECC)--(68.1 +/- 6.7 mumol/l) was measured, as well as nitrite concentration in the coronary circulation before and after construction of the IMA bypass graft (62.1 +/- 4.19 mumol/l and 50.26 +/- 4.0 mumol/l respectively). Furthermore, nitrite level in the IMA graft free cut end flow was also determined (64.3 +/- 5.9 mumol/l). These data compared to the nitrite levels in the normal plasma (48.1 +/- 5.9 mumol/l) were found to be higher (p = 0.1, ns.), possibly due to the enhanced EDNO production induced by total heparinization. The nitrite concentration in the IMA free cut end flow is similar or slightly higher than that of the native coronary circulation, however, after IMA bypass construction a relative reduction could be measured in the coronary sinus. Authors believe, that this may be related to the reduction of basal EDNO production caused by supernormal pO2 (215 +/- 19 mmHg) during ECC.

Adult↗
PubMed1999

Inferring perceptual saliency fields from viewpoint-dependent recognition data.

We present an algorithm for computing the relative perceptual saliencies of the features of a three-dimensional object using either goodness-of-view scores measured at several viewpoints or perceptual similarities among several object views. This technique addresses the inverse, ill-posed version of the direct problem of predicting goodness-of-view scores or viewpoint similarities when the object features are known. On the basis of a linear model for the direct problem, we solve the inverse problem using the method of regularization. The critical assumption we make to regularize the solution is that perceptual salience varies slowly on the surface of the object. The salient regions derived using this assumption empirically indicate what object structures are important in human three-dimensional object perception, a domain where theories typically have been based on somewhat ad hoc features.

Algorithms↗
PubMed1998

Photomodification of cardiac membrane: chaotic currents and high conductance states in isolated patches.

We have demonstrated previously that photomodification permeabilizes cardiac cells as evidenced by activation of a whole-cell leak current. In this paper we report that photomodification induces in cell-attached and inside-out cardiac membrane patches a chaotic current. Unlike current recordings from many protein ion channels that show stepwise amplitude changes associated with open and closed states of the channel, the chaotic current consists of variable amplitude spike-like transitions. The amplitudes of these spikes can vary from tenths to tens of picoamperes at a constant transmembrane potential. We provide evidence that the chaotic current is transmembrane rather than trans-seal and has a voltage dependency expected for current flow through nonspecific conductance pathways. Photomodification can also induce high conductance states (greater than 500 pS) in cell-attached and inside-out patches. We present evidence that the high conductance state is also not related to seal breakdown. Our results suggest that both the chaotic current activity in and high conductance state of photomodified cardiac membrane patches result from the opening of many small conductance, nonspecific pathways through the membrane.

Animals↗
PubMed1998

GH3 cells, ionic currents and cell killing: photomodification sensitized by Rose Bengal.

Photosensitization using Rose Bengal (RB) modifies membrane ionic currents and kills cultured mouse pituitary, GH3, cells. Here we investigate the dose-response relationship for ionic current modification and for cell killing to assess a possible causal link. When exposed to 0.5 microM RB and 6.5 mW/cm2 of visible light, calcium current was blocked in 1.9 +/- 0.2 min (mean +/- SEM; 0.74 +/- 0.08 J/cm2; n = 18), a transient component of potassium current, tentatively identified as a delayed-rectifier potassium current, disappeared in 52 +/- 8 s (0.34 +/- 0.05 J/cm2; n = 10) and a steady-state component of potassium current, largely a calcium-activated potassium current, disappeared in 3.5 +/- 0.4 min (1.37 +/- 0.16 J/cm2; n = 11). Conversely, the background leak current increased in magnitude. At 5 min of illumination, the longest time studied here, it continued to increase nearly linearly, making it the only current component studied that is still changing after 5 min of light. Under the conditions used, cell killing increased to 100% in the exposure range of 4-10 min of illumination (1.6 J/cm2 to 3.9 J/cm2) when assessed using fluorescent markers, ethidium homodimer and calcein and required slightly longer exposure times when assessed using trypan blue. Thus, it is difficult to ascribe a causal role in cell killing by photosensitization to alterations of standard ion channels and known ionic currents. However, the increase in leak current has the correct dose-response characteristics to be involved.

Animals↗
PubMed1995

Progression of cardiac potassium current modification after brief exposure to reactive oxygen.

We reported previously that singlet oxygen (1O2), generated by illuminating the photosensitizer rose bengal (RB), suppressed the delayed rectifier potassium current (IK) in single frog atrial cells. Considering the brief lifetime of 1O2, one might expect IK modification to reach a steady-state soon after a brief exposure to RB-generated 1O2. Here we report that, contrary to expectations, tens of seconds can be required for IK to reach a new steady-state. We will use the term "progression" to refer to the component of current modification which occurs after cessation of illumination. To gain insight into the mechanism of progression, we investigated how its time course and magnitude were affected by (1) membrane potential during and following RB illumination, and (2) the level of IK activation during illumination. We found that conditions which favored the open state of the potassium channel also favored progression, increasing both its time course and magnitude. Illumination while IK was activated produced significant progression having a very slow time course (tens of seconds). By comparison, illumination when IK was not activated produced no progression: IK modification was completed during the 2 s illumination period. These findings suggest progression results from the kinetics of potassium channel state transitions rather than from a long-lived reactive intermediate produced during the initial 1O2 exposure.

Animals↗
PubMed1994

Properties of cardiac I(leak) induced by photosensitizer-generated reactive oxygen.

We reported previously that photomodification of single frog cardiac cells by Rose Bengal induces a time-independent current, designated I(leak)++, having a linear current-voltage (I/V) relationship. The purpose of the present study is to better characterize the properties of I(leak)++. Initially, I(leak)++ has a reversal potential (ER) near -70 mV, but with time, ER shifts toward a final value near 0 mV. This shift in ER is accompanied by a marked increase in conductance (slope of I/V relationship). Evidence is presented that the depolarizing shift in ER with time during photomodification results from a loss of membrane selectivity allowing sodium to make an increasing contribution to I(leak)++. Potassium also contributes to I(leak)++, as indicated by marked depolarizing shifts in ER following replacement of intracellular potassium with either cesium or tetraethylammonium. Since these results occur in calcium-free external media, the depolarizing shifts in ER and increased conductance are not related to activation of a calcium-dependent nonselective cation channel. However, I(leak) does have some properties similar to nonselective cation currents recently reported to be activated by membrane breakdown products such as arachidonic acid and lysophosphoglycerides.

Animals↗
PubMed1994

Membrane ionic current photomodification by rose bengal and menadione: role of singlet oxygen.

Photosensitized modification of ionic leak current and potassium current was studied in frog cardiac atrial cells using whole cell patch clamp techniques. Rose bengal (RB) and menadione (MQ) were used as photosensitizers. Separate photophysical studies of the photosensitizers in deuterium oxide solution demonstrated that MQ did not produce singlet oxygen as evidenced by the lack of luminescence at 1270 nm, whereas RB was an efficient singlet oxygen generator. Both photosensitizers sensitized block of potassium current in atrial cells, and both sensitized an increase of ionic leak current. However, when photosensitizer concentrations and illumination intensities were adjusted to match the rate of block of potassium current by the two photosensitizers, there were dramatic differences in leak current increase, both quantitatively and qualitatively. Menadione sensitized a much slower increase in leak current than did RB. Further, the leak current sensitized by MQ had a more positive reversal potential than that sensitized by RB, suggesting a less potassium-selective leak current pathway. The results suggest that, while the effects of singlet oxygen and non-singlet oxygen modification of cell membranes may be similar, there may also be significant differences in the resulting membrane permeabilities. The results also demonstrate that MQ and RB may be useful agents to study the role of singlet oxygen versus non-singlet oxygen modification of biological systems.

Animals↗
PubMed1993

Membrane potential can influence the rate of membrane photomodification.

Though cellular photomodification has been shown to change cellular resting membrane potential, an effect of membrane potential on the rate of photomodification has never been reported. Here we demonstrate that the rate of photomodification of potassium channels in frog atrial cells is voltage dependent. The rate of potassium channel photomodification using negatively charged Rose Bengal as the photosensitizer is about 2.5 times greater at the resting membrane potential of -70 mV compared to +40 mV. Similar results are obtained using the positively charged photosensitizer methylene blue. On the other hand, the rate of photomodified increase of leak current in the same cells does not significantly change in this voltage range with Rose Bengal as photosensitizer, but demonstrates a voltage dependence like that of potassium current when methylene blue is the photosensitizer. These observations cannot be explained based on voltage-dependent partitioning of the sensitizer, as similar effects on potassium current were obtained using either a positively charged or negatively charged sensitizer.

Animals↗
PubMed1991

Modification of cardiac ionic currents by photosensitizer-generated reactive oxygen.

The effects of reactive oxygen species (ROS) generated by light and the photosensitizer Rose Bengal on ionic currents in single frog atrial cells were investigated. The excitatory inward sodium and calcium currents were both suppressed by ROS as was the outward, delayed rectifier potassium current. The inactivation kinetics of the sodium current were slowed markedly whereas the kinetics of calcium current inactivation were much less affected and potassium current activation was not changed. The sodium current-voltage relationship was shifted in the depolarizing direction by ROS whereas the voltage-dependencies of both the calcium and potassium currents were not affected. In addition to suppressing the time- and voltage-dependent sodium, calcium, and potassium currents, ROS enhanced a time-independent current which was outwardly directed at positive membrane potentials. However, the induction of this time-independent current required longer ROS exposure than was required to significantly suppress the other currents. The rapid onset of ROS-induced suppression of calcium and potassium currents followed by a later enhancement of a time-independent current can explain ROS-induced changes in action potential duration. Brief ROS exposure increased action potential duration whereas longer exposure reduced action potential duration.

Action Potentials↗
PubMed1991

Membrane photomodification of cardiac myocytes: potassium and leakage currents.

Cardiac myocytes were isolated from the atria of frogs (Rana pipiens) and whole cell potassium (IK) and "leakage" (Ileak) currents were monitored using the patch clamp technique. Cells were photosensitized by exposure to Rose Bengal (0.125-0.5 microM). Illumination produced an exponential decrease in IK, and an increase in Ileak. Current modifications varied with light intensity and sensitizer concentration. IK stabilized when illumination ceased, while Ileak continued to increase at a slower rate after illumination ended. The exponential nature of IK modification suggests that potassium channels are photomodified with single hit kinetics. The stabilization of IK following illumination suggests (1) that the photomodification of the potassium channel does not involve long lasting (minutes) radical chain reactions and (2) that this photomodification is not repaired in the course of a few minutes.

Animals↗
PubMed1990

Inhibition of transcription by adriamycin is a consequence of the loss of negative superhelicity in DNA mediated by topoisomerase II.

Adriamycin is commonly used as a chemotherapeutic agent and is known to intercalate into the major groove of DNA and inhibit DNA and RNA synthesis. Results presented in this communication suggest that adriamycin affects topoisomerase cleavage of DNA. The resultant change in negative superhelicity (decrease) is responsible for the decrease in transcription. This process is not dependent on the continued presence of adriamycin. The reaction between topoisomerases, DNA and adriamycin is dose-dependent. The results help to explain the relatively enhanced cytotoxicity of this drug to tumor cells.

Animals↗
PubMed1989

Intracellular magnesium affects I(K) in single frog atrial cells.

Voltage-clamp experiments on single frog (Rana pipiens) atrial cells using whole cell recording techniques revealed that the addition of MgCl2 to the 150 mM KCl patch pipette solution influenced the voltage- and time-dependent potassium current (IK). After rupture of the membrane patch under the tip of the pipette, IK increased with time when the pipette solution was magnesium free, but decreased slightly when the solution contained 1.5 mM MgCl2. More dramatic decreases in IK occurred when the solution contained 3.0 or 10 mM MgCl2. In addition to suppressing the magnitude of IK, the activation rate of this current was enhanced by 10 mM MgCl2 but was not affected by 1.5 or 3 mM MgCl2. Other chloride salts containing mono-, di-, or trivalent cations were used to demonstrate that the effects of MgCl2 on IK were not related to alterations in ionic strength, osmolality, or chloride concentration produced by adding MgCl2 to the pipette solution. Our results suggest that changes in the intracellular magnesium concentration influence IK as the pipette solution exchanges with the intracellular fluid.

Animals↗
PubMed1987

Neuropharmacology of a new psychotropic 2,3-benzodiazepine.

1-(3-Chlorophenyl)-4-methyl-7,8-dimethoxy-5H-2,3-benzodiazepine (GYKI 51189) is a new analogue of tofisopam. Due to the novel chemical structure this molecule displays a peculiar spectrum of pharmacological activity. In many respects tofisopam and its new analogue differ from the traditional 1,4-benzodiazepines, e.g. in that they possess selective anxiolytic action without muscle relaxant and anticonvulsive activity, as well as they do not show any affinity for the 1,4-benzodiazepine receptors. This new compound exerts more pronounced anxiolytic potency than tofisopam. In addition to its main action it possesses significant antidepressant activity. It attenuates psychomotor agitation and exerts significant antiaggressive effect by reducing both spontaneous and induced aggressiveness. Vegetative responses (rise in blood pressure and heart rate) induced by electric stimulation of the hypothalamus are also inhibited by this compound, while motor functions remain unaffected and no somnolence is induced. The new tofisopam analogue fails to exert any potentiating effect either on ethanol or on barbiturates. GYKI-51189 has a highly favourable therapeutic index and only few side effects. Neither tolerance nor dependence was observed during the chronic toxicological investigations.

Aggression↗
PubMed1986

Voltage-tension relations in single frog atrial cardiac cells.

Voltage-clamp experiments were performed on isolated single frog (Rana catesbeiana or Rana pipiens) atrial cells to determine the voltage-contraction relations of the single cardiac cell. The contractile responses of the single cell associated with long duration (3 second) depolarizing steps consisted of a rise to peak (phasic) followed by a decay to a sustained contraction (tonic). These phasic-tonic type contractile responses could be obtained under conditions where membrane potential was well controlled along the entire length of the cell. Thus, the data obtained on the single cell indicate that the phasic-tonic contractile response is the characteristic contractile response of frog atrial tissue. The voltage dependence of the extent of relaxation to the tonic component following the peak of the contraction was affected dramatically by the intracellular sodium concentration. This result indicates that both the relaxation following peak contraction as well as the tonic contraction are related to calcium control via the sodium-calcium exchanger. The data also indicate that calcium entry via the inward calcium current is required for the contractile response to have a phasic component. These data indicate that calcium entry via the inward calcium current followed by the sodium-calcium exchanger first reducing and then maintaining the intracellular calcium level produces the characteristic phasic-tonic contractile response.

Animals↗
PubMed1985

A stochastic approach in the evaluation of plasma curves with enterohepatic recycling.

The precision of the existing methods for evaluation of compartmental models may not be warranted if the plasma curve is irregular due to enterohepatic recycling of the substance during its elimination. In this work a new approach is proposed which involves the assessments of rate-constants using combined cross-sectional and time-series data. As (C0-Cpl) means the concentration of the drug in the environmental compartment, the (Formula: see text) equation is valid for the change in the plasma concentration level. Calculating the correlation coefficients (r) for the Cpl and (C0-Cpl) data-pairs from the cross-sectional data, in this case the time-derivatives of these correlation coefficients are equal to the rate constants.

Animals↗
PubMed1984

Depression of contractility following stretches and releases applied during contraction to single frog atrial cardiac cells.

The effects of stretches and releases on the contractile performance of isolated single frog atrial cells (Rana catesbeiana) were investigated. A stretch or release was imposed on the cell--either during a contraction (test) or before the onset of contraction (control)--and the contractile performance (length, velocity and force) of the test contraction was compared with that of the control contraction to determine whether the stretch or release imposed on the contracting cell altered the contractility of the cell. We found that the velocity of cell (and sarcomere) shortening for the remainder of the test contraction following either a stretch or release was markedly less than that occurring at the same time in the control contraction. This decreased velocity occurred even though the force in the test contraction was less than that in the control contraction and the sarcomere length was longer in the test contraction than in the control contraction. These results indicate that after a stretch or release imposed on the contracting cell, the force-velocity relationship at any given length and time is depressed than had the stretch or release not been imposed on the contracting cell. Thus, stretches and releases applied to the contracting single cardiac cell either produce a long-term depression in the contractility of the cell, or that the contractility at any given time and sarcomere length depends markedly on the history of the contraction.

Animals↗