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M R Mitchell

Publications and source records attributed to M R Mitchell.

11 recordsLinked to original sources
PubMed1988

Effect of lidocaine on action potentials, currents and contractions in the absence and presence of ouabain in guinea-pig ventricular cells.

The effects of lidocaine have been investigated on electrical and contractile activity in guinea-pig ventricular cells in the absence and in the presence of ouabain. At low (therapeutic) doses, lidocaine induced a small reduction in action potential duration and contraction but had no effect on transient depolarizations or, under voltage-clamp conditions, on the transient inward currents. At much higher concentrations of lidocaine (greater than 500 microM), where the fast inward sodium current was substantially blocked, there was also a marked reduction in the amplitude of the calcium current and accompanying phasic contraction. Again, lidocaine did not inhibit the transient depolarizations or transient inward currents. This suggests that there is no direct effect of lidocaine on the calcium-induced release of calcium from the sarcoplasmic reticulum and that lidocaine does not indirectly inhibit arrhythmic activity by reducing intracellular sodium in the isolated ventricular cell. Possible mechanisms for the antiarrhythmic action of lidocaine in whole heart are discussed.

Action Potentials↗
PubMed1987

Electrical activity and contraction in cells isolated from rat and guinea-pig ventricular muscle: a comparative study.

1. Contraction in single ventricular muscle cells from rat and guinea-pig heart was measured using an optical technique, while at the same time either action potentials were recorded or transmembrane currents were measured under voltage-clamp conditions. 2. When the membrane was depolarized to 0 mV, there was a phasic and a tonic component of the contraction in guinea-pig cells, whereas in rat cells only the phasic component was obvious. In both species the depolarizations evoked the second inward current (Isi). 3. In rat cells, when the membrane potential during a depolarization was varied over the range -40 to +60 mV, the amplitude of contraction first increased to a peak at a potential close to 0 mV, and then declined as the membrane potential became more positive. In contrast, contraction in guinea-pig cells measured under similar conditions continued to increase as the depolarization was increased, and the tonic component of contraction became more obvious at more positive potentials. Contraction amplitude in guinea-pig cells could also be increased by increasing pulse duration under conditions where the tonic component of contraction was prominent. 4. Contraction during depolarization was suppressed by ryanodine in rat cells, whereas in guinea-pig cells contraction persisted, but with a modified time course. Ryanodine did inhibit spontaneous contractions of guinea-pig cells during exposure to low extracellular sodium. 5. Nifedipine suppressed Isi and phasic contraction in both rat and guinea-pig cells. In guinea-pig cells these effects developed contemporaneously, but in rat cells substantial reduction of Isi occurred before marked suppression of contraction. 6. In rat cells exposed to strontium in place of external calcium, inactivation of Isi was slowed and contraction was prolonged, with a slower time-to-peak and relaxation. The time course of the action potential was modified and ryanodine no longer inhibited contraction of rat cells in the presence of strontium. 7. It is concluded that the amplitude of contraction in rat and guinea-pig ventricular cells is determined by calcium both entering through the surface membrane and released from internal stores, and that under normal conditions the balance is towards release from stores in rat cells, and towards entry through the surface in guinea-pig cells.

Action Potentials↗
PubMed1987

Calcium-activated inward current and contraction in rat and guinea-pig ventricular myocytes.

1. Single ventricular cells from rat and guinea-pig hearts were voltage clamped, and contraction was monitored with an optical method. 2. In rat cells, short (2-10 ms) depolarizing pulses to 0 mV from a holding potential of -40 mV evoked current carried by calcium, and on repolarization to -40 mV there was a slow 'tail' current which decayed much more slowly than the expected deactivation of calcium current at this potential. 3. When rat cells were loaded with EGTA diffusing into the cytosol from an intracellular electrode, contraction and the tail current were both abolished, whereas the peak calcium current was not reduced. 4. Exposure of rat cells to ryanodine (1-2 microM) suppressed both contraction and the tail current, but not peak calcium current. 5. The tail current was unaffected by tetrodotoxin (10 microM), but was reduced by lowering extracellular sodium to 10% by replacement with lithium or choline. 6. In rat cells, exposure to nifedipine (1-5 microM) initially caused a marked reduction of calcium current while substantial contraction and tail current remained; longer exposure to nifedipine suppressed both contraction and the tail current. Isoprenaline (50-100 nM) caused a marked increase in peak calcium current, while under these conditions there was little or no increase in either contraction or tail current. 7. The amplitude of the tail current in rat cells varied with the duration of the depolarization at 0 mV; the tail current evoked by repolarization to -40 mV reached a peak just as contraction was beginning to develop and was back to undetectable levels just as relaxation became significant, as might be expected if the tail current were determined by the cytosolic calcium transient which triggered contraction. 8. In guinea-pig cells, a tail current was also recorded on repolarization to a holding potential of -40 mV, and, as in rat cells, the tail was suppressed by cytosolic EGTA and reduced by exposure of the cells to low-sodium solution. 9. It is concluded that the tail currents recorded in both rat and guinea-pig cells represent current activated by a rise in cytosolic calcium; in rat cells this is markedly dependent on ryanodine-sensitive release of calcium from internal stores. The origin of this current, and its possible role during the plateaux of action potentials are discussed.

Action Potentials↗
PubMed1986

Improved determination of spin density, T1 and T2 from a three-parameter fit to multiple-delay-multiple-echo (MDME) NMR images.

A method is presented for simultaneously determining values of relative hydrogen spin density Nr, T1 and T2 from a single set of NMR image intensities acquired in a short imaging time. Present methods use separate acquisitions and data sets to determine all three parameters. In the method presented, multiple-echo data are collected at multiple delays in virtually the same imaging time used to obtain T1 and a T2-weighted Nr from a separate saturation recovery (SR) T1 measurement. All three parameters are then determined by a three-parameter fit of a derived signal intensity equation to these multiple-delay-multiple-echo (MDME) data. This provides an inherent correction of Nr for T1 and T2 weighting without the use of sequences with TD greater than 5T1, and without further data collection for a separate T2 measurement. It also provides an effective reduction in the noise of the separate T2 measurement. A three-parameter fit to MDME data appears to be superior to the separate T1 and T2 measurements currently used to determine all three parameters. Calculations performed on CrCl3 solutions produced T1 values from 21 ms to 3.4 s, T2 values from 6 to 714 ms, and standard errors as low as 0.33%, with a net imaging time of the order of that required for routine low-noise signal intensity imaging. The method could potentially be used in NMR spectroscopy to give similar benefits.

Animals↗
PubMed1986

Electrical properties and response to noradrenaline of individual heart cells isolated from human ventricular tissue.

The analysis of the electrical properties and response to catecholamines of cardiac tissue is greatly simplified by the use of single cell preparations. In this study individual cells isolated from human ventricular tissue were used to estimate cellular sarcolemmal resistance and capacitance and to record the time course of the response to ionophoretically applied noradrenaline. The mean input capacitance of the cells is consistent with a surface membrane area of approximately 15,000 micron2 if the specific membrane capacitance is 1 microF X cm-2. This is larger than might be expected from the measured external dimensions of the cell and is compatible with the presence of surface membrane infoldings and caveolae. At membrane potentials close to -75 mV the mean cell input resistance was approximately 40 M omega, giving a specific membrane resistance of 6 omega X cm2 if mean membrane area is 15,000 micron2 and consistent with the assumption that the isolated cells have sealed intercalated discs under the experimental conditions used. Ionophoretically applied noradrenaline produced a pronounced prolongation of the plateau phase of the action potential, but this effect developed over many seconds. The slow onset of action is not compatible with the kinetics of free extracellular diffusion of catecholamine but may reflect molecular events that occur between noradrenaline binding to membrane receptors and the final cellular response. Under voltage-clamp conditions, the cells showed a time dependent inward current consistent with the rapid activation and decay of a sarcolemmal calcium conductance.

Action Potentials↗
PubMed1986

Enhancement of red blood cell proton relaxation with chromium labeling.

Nuclear medicine has utilized chromium (Cr) for decades to label red blood cells (RBCs). The purpose of this project was to determine whether sufficient paramagnetic Cr could be bound to red cells to influence proton relaxation significantly. We demonstrated that the T1 and T2 of RBCs can be substantially shortened by labeling them with paramagnetic Cr. Proton relaxation enhancement occurs when red cells are incubated with sodium chromate (VI) over a concentration range of 0.10 mM to 31.6 mM. Labeling with Cr at a concentration of 31.6 mM shortened the T1 of packed cells from 714 msec to 33 msec, and the T2 from 117 msec to 24 msec, as compared with nonlabeled red cells. In vitro hemolysis was significantly increased after labeling at 31.6 mM, but not at lower concentrations. Cr-induced proton relaxation enhancement varied with RBCs from different species, temperature, pH, and length of incubation. T1 values of kidneys containing labeled red cells (303 msec), or labeled cells diluted 10-fold with nonlabeled cells (479 msec), were decreased compared with kidneys containing only nonlabeled cells (600 msec). Finally, preliminary data indicate that the signal intensity of perfused renal tissue is significantly influenced in vivo by infusion of Cr-labeled RBCs. This study demonstrated that Cr labeling of RBCs sufficiently enhances red cell proton relaxation to provide excised organs containing red cells, of which 10% have been Cr-labeled, with shorter T1 and T2 values than organs containing nonlabeled cells. In addition, the ability of labeled cells to alter signal intensity in vivo suggests that Cr may have the potential to become an MRI contrast agent.

Animals↗
PubMed1985

Influence of a change in stimulation rate on action potentials, currents and contractions in rat ventricular cells.

The effects of a change in stimulation rate on electrical activity and accompanying contraction were investigated in ventricular cells isolated from rat heart; the cells were stimulated to contract either by brief depolarization pulses which evoked action potentials, or, under voltage-clamp conditions, by step depolarizations. An increase in stimulation rate from 0.3 to 3 Hz resulted in a gradual reduction in the amplitude of contraction and attenuation of the late phase of the action potential. These changes were less marked at more depolarized potentials. The ventricular cells were voltage clamped at -40 mV and initially stimulated at 0.3 Hz by step depolarizations to 0 mV for 10 or 100 ms, which activated the second inward current (Isi) and an accompanying contraction. The amplitude and time course of contraction were similar with the two pulse durations. When the duration of the depolarization was 100 ms, an increase in stimulation rate to 3 Hz caused a gradual decline in the amplitude of Isi and of the evoked contraction; at the same time extra contractions and small, transient inward currents appeared in addition to the evoked contractions and Isis. There was a reduction in the early component of decay of Isi at 3 Hz. With a depolarizing pulse duration of 10 ms, an increase in stimulation rate to 3 or to 4.2 Hz did not change the amplitude of the evoked Isi or contraction and no extra contractions or currents appeared. Intracellular EGTA abolished all contractions in the cells and an increase in the rate of stimulation with 100 ms pulses did not then induce transient inward currents. There was some decrease in the Isi amplitude but this was not as marked as in the absence of EGTA and the time course of current decay was similar at the two rates. Ryanodine prevented the appearance of extra contractions and currents when the stimulation rate was increased to 3 Hz and, as in the presence of intracellular EGTA, there was a small decrease in Isi amplitude while the time course of decay was similar at the two stimulation rates. The time course of recovery of Isi from inactivation, as shown by a double-pulse procedure, was altered when the duration of the first pulse was reduced from 100 to 10 ms, an extra inactivation of Isi being seen at pulse intervals of 20-100 ms. This extra component of inactivation was not seen with intracellular EGTA or in the presence of ryanodine.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗