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Biomedical subjects

T Powell

Publications and source records attributed to T Powell.

At least 91 records · Page 5Linked to original sources
PubMed1989

Calcium movements during each heart beat.

Transsarcolemmal calcium movements are closely related to force generation in the heart. It is important to understand the transport pathways that control these movements of calcium across the sarcolemmal membrane. In the normal, beating heart, sodium-calcium exchange appears to be an important mechanism for the extrusion of calcium from the cell. The kinetics of this exchange are dependent upon the characteristics of the cell action potential. Calcium efflux via sodium-calcium exchange may be sufficient to balance calcium entry through calcium channels during the action potential.

Action Potentials↗
PubMed1989

Li+ inhibition of membrane current responses to epinephrine in guinea-pig ventricular cells.

Membrane currents of guinea-pig ventricular myocytes were recorded using the whole-cell voltage clamp method. The epinephrine-induced increase in Ca2+ current (2.9 +/- 0.5 times control) was reduced (1.8 +/- 0.3 times) by replacing Na+ with Li+ in the bathing solution. In addition, 0.5 microM epinephrine increased a time-independent membrane conductance in the Na+ external solution, having a reversal potential of -19 +/- 3 mV (epinephrine-induced current). In the Li+ external solution, however, 0.5 microM epinephrine failed to induce the epinephrine-induced current. The findings are consistent with the reported Li+ inhibition of GTP-binding protein and/or adenylate cyclase.

Animals↗
PubMed1989

Prolapsed thoracic intervertebral disc: the importance of CT assisted myelography.

We present six new cases of prolapsed thoracic intervertebral disc (PTIVD), and review the clinical and radiological features, particularly with regard to the role of computed tomography (CT) examination in the diagnosis and management. In patients with atypical lower limb pain, particularly when associated with sphincter disturbances, lumbar myelography is incomplete unless supplemented by an examination of the conus region and lower thoracic cord. The supplementary use of CT in suspected PTIVD is of considerable value to the surgeon in determining the size, position, and volume of the sequestration, and the extent of excavation of the spinal cord by prolapsed disc material.

Aged↗
PubMed1989

Evidence of reduced 'cognitive inhibition' in schizophrenia.

An experiment is described which investigated cognitive inhibition in schizophrenia. It is noted that both the abnormal and cognitive literatures use the concept of inhibition. Frith (1979) suggests that the more cognitive symptoms of schizophrenia may be due to the failure to limit the current contents of consciousness due to a failure adequately to inhibit the output of preconscious processes. Current thinking in cognitive psychology suggests that in the process of selective attention there is active inhibition of distractor information. A technique used to investigate this is termed negative priming (Tipper, 1985). The general nature of this paradigm is as follows: if a distractor, which has been previously ignored, is response, due to inhibition of the information when it was originally a distractor. It was found that inhibition of such distracting information was reduced in schizophrenics. This finding is seen as providing some support for Frith's (1979) theory that the cognitive symptoms of schizophrenia are due to awareness of processes that normally occur preconsciously.

Adult↗
PubMed1989

Sodium-calcium exchange during the action potential in guinea-pig ventricular cells.

1. Slow inward tail currents attributable to electrogenic sodium-calcium exchange can be recorded by imposing hyperpolarizing voltage clamp pulses during the normal action potential of isolated guinea-pig ventricular cells. The hyperpolarizations return the membrane to the resting potential (between -65 and -88 m V) allowing an inward current to be recorded. This current usually has peak amplitude when repolarization is imposed during the first 50 ms after the action potential upstroke, but becomes negligible once the final phase of repolarization is reached. The envelope of peak current tail amplitudes strongly resembles that of the intracellular calcium transient recorded in other studies. 2. Repetitive stimulation producing normal action potentials at a frequency of 2 Hz progressively augments the tail current recorded immediately after the stimulus train. Conversely, if each action potential is prematurely terminated at 0.1 Hz, repetitive stimulation produces a tail current much smaller than the control value. The control amplitude of inward current is only maintained if interrupted action potentials are separated by at least one full 'repriming' action potential. These effects mimic those on cell contraction (Arlock & Wohlfart, 1986) and suggest that progressive changes in tail current are controlled by variations in the amplitude and time course of the intracellular calcium transient. 3. When intracellular calcium is buffered sufficiently to abolish contraction, the tail current is abolished. Substitution of calcium with strontium greatly reduces the tail current. 4. The inward tail current can also be recorded at more positive membrane potentials using standard voltage clamp pulse protocols. In this way it was found that temperature has a large effect on the tail current, which can change from net inward at 22 degrees C to net outward at 37 degrees C. The largest inward currents are usually recorded at about 30 degrees C. It is shown that this effect is attributable predominantly to the temperature sensitivity of activation of the delayed potassium current, iK, whose decay can then mask the slow tail current at high temperatures. 5. Studies of the relationship between the tail current and the membrane calcium current, iCa, have been performed using a method of drug application which is capable of perturbing iCa in a very rapid and highly reversible manner. Partial block of iCa with cadmium does not initially alter the size of the associated inward current tail. When iCa is increased by applying isoprenaline, the percentage augmentation of the associated tail current is much greater but occurs more slowly.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1989

Fate of gap junctions in isolated adult mammalian cardiomyocytes.

The fate of gap junctions in dissociated adult myocytes, maintained for up to 22 hours in culture medium, was investigated by semiquantitative analysis of thin sections and by freeze-fracture electron microscopy. Gap junctions in the dissociated myocyte are intact bimembranous structures seen either as invaginated surface-located structures or as annular profiles in the cytoplasm. Surface-located junctions are sealed from the exterior by a sheet of nonjunctional membrane originating (together with the "outer" junctional membrane) from the formerly neighboring cell. Serial sectioning was used to establish that at least part of the annular gap junction population in the freshly isolated myocyte represents truly discrete cytoplasmic vesicles; thus, some gap junctions are rapidly endocytosed after myocyte separation. Analysis of the surface-located-to-annular gap junction ratio suggested that no further endocytosis occurred in rabbit and cat myocytes maintained for 22 and 15 hours, respectively. Guinea pig myocytes, by contrast, did appear to continue endocytosis in culture. Analysis of the distance of gap junctional structures from the cell surface suggested that little if any inward migration of gap junction vesicles occurred. Hypoxia had no detectable effect on the internalization or inward movement of gap junctions. The quantity of ultrastructurally detectable gap junction membrane appeared to remain constant over time, as did the incidence of "complex structures" (i.e., annular gap junction profiles with features previously suggested to represent degradation). New gap junction formation was negligible, and a reappraisal of the nature of "complex structures" led to the conclusion that the origin of these structures need not be related to degradation. Taken together, the findings suggest that degradation and disappearance of gap junctional membrane after isolation of the mature myocyte constitute a much slower process than previously believed, and the possibility that the cardiac gap junction protein has a longer half-life than its counterpart in liver remains open.

Animals↗
PubMed1988

Alteration of inositol phospholipid metabolism in rat cortex by lithium but not carbamazepine.

The effect of carbamazepine on inositol phospholipid metabolism was investigated in rat cerebral cortex. The stimulation of inositol phosphate formation by 5-HT (10 microM), carbachol (100 microM) and noradrenaline (30 microM) was not significantly altered by carbamazepine in vitro. 14 days treatment of rats in vivo with carbamazepine was similarly without effect on these parameters. In contrast 14 days treatment with LiCl reduced the agonist responses by 25-50%. The results are discussed in relation to the therapeutic actions of these drugs.

Animals↗
PubMed1988

On the mechanism of isoprenaline- and forskolin-induced depolarization of single guinea-pig ventricular myocytes.

1. Isoprenaline (10 nM to 1 microM) and forskolin (0.6-100 microM) depolarized single guinea-pig myocytes studied in vitro. Under voltage clamp both agents caused an inward current to flow. 2. These effects were abolished by propranolol (100 nM) and the beta1-antagonist metoprolol (100-200 nM), but not by the beta2-agonist [corrected] salbutamol (1 microM). 3. The interaction of isoprenaline with forskolin, caffeine or isobutylmethylxanthine (IBMX) on current amplitude was as expected if all of these drugs were causing inward current by increasing intracellular levels of cyclic adenosine monophosphate (cyclic AMP). Low concentrations of forskolin (less than 600 nM) or IBMX (less than 20 microM) potentiated the effect of isoprenaline, whereas isoprenaline caused no further inward current in cells in which high concentrations of forskolin (600 nM-100 microM) or IBMX (20 microM-1 mM) were already evoking maximum inward current. 4. Isoprenaline-induced inward current was reduced 30-50% by acetylcholine (10-30 microM). This action of acetylcholine was blocked by atropine (100 nM). 5. The effect of isoprenaline on holding current was critically dependent on temperature. The onset of the current was delayed and its amplitude reduced as the myocyte was cooled from 37 degrees C to ambient temperature (22-24 degrees C). 6. Isoprenaline-induced inward current was not affected by the potassium channel blockers barium (2 mM) or tetraethylammonium (TEA; 10-20 mM). The amplitude of the inward current did not vary as a function of [K+]o. 7. The inward current was not affected by the calcium channel blockers cadmium 1 mM, or nifedipine (10 microM), or when internal calcium was reduced by including EGTA in the recording electrode filling solution. 8. The amplitude of the current was also unaffected by caesium (5 mM), which blocks the hyperpolarization-activated, non-specific channel if, or by strophanthidin (10 microM) which blocks the Na+-K+ pump. It was unchanged by substitution of external chloride by isethionate. 9. The inward current was absent when external sodium was replaced by the impermeant ion tetramethylammonium (TMA). 10. Isoprenaline- and forskolin-induced inward currents were associated with an increase in both membrane chord conductance and noise. The increase in conductance was most readily measured at potentials where the inwardly rectifying potassium channel, iK1, was small, or when iK1 was blocked by the addition of barium (2 mM).(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗
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

Determination of intracellular potassium ion concentration in isolated rat ventricular myocytes.

The sarcoplasmic potassium concentration of a suspension of rat ventricular myocytes, prepared by collagenase-induced disruption of the myocardial mass, was determined by a null-point technique. Addition of digitonin resulted in a release of potassium from the cells which was interpreted as a flux from the sarcoplasm. The intracellular potassium concentration was estimated to be 113 +/- 6mM.

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↗
PubMed1985

Single cells and rapid inward sodium current.

This chapter presents a brief review of measurements of rapid inward sodium current in single cardiac cells. It is shown that the simplified morphology of the individual cells, with a lack of restricted extracellular space, has been exploited to provide improved spatial and temporal voltage control, resulting in the first recordings of both the activation and inactivation phases of rapid inward sodium current. It is to be expected that future research will produce much interesting data on this component of membrane current, which will have direct relevance to many processes concerned with cardiac function at the cellular level.

Animals↗
PubMed1985

Isolated adult heart cells. The development of a new experimental model.

The isolation and characterization of calcium-tolerant cells from adult myocardial tissue has proved a major new field of heart research. The wide range of problems which can be examined using single cells in suspension offers the possibility of investigating many important mechanisms underlying diseased states in the myocardium.

Animals↗
PubMed1985

Electrophysiological properties of isolated ventricular myocytes.

There is no doubt that major advances have been made in cardiac electrophysiology using single heart cells. Accurate analysis of rapid inward sodium current and the second inward current carried by calcium has resulted in a major re-examination of the steps involved in excitation-contraction coupling in the heart. Future work using glass microelectrodes, suction pipettes and patch pipettes will yield a vast amount of information highly relevant to mechanisms involved in the initiation of the heartbeat.

Animals↗
PubMed1985

Morphometric analysis of the isolated calcium-tolerant cardiac myocyte. Organelle volumes, sarcomere length, plasma membrane surface folds, and intramembrane particle density and distribution.

Using morphometric analysis of thin sections and freeze-fracture replicas, the ultrastructure of isolated rat myocytes prepared by collagenase digestion (Powell et al. 1980) was compared with that of myocytes fixed by perfusion of intact myocardium. The volumes of myofibrils, mitochondria, nuclei, sarcoplasmic reticulum and lipid droplets in the isolated myocytes did not differ from those of their counterparts in the intact heart, but the volume occupied by transverse tubules was apparently reduced. The isolated cells had significantly shorter sarcomeres than did cells in the intact tissue, and this was associated with an altered topography of plasma membrane surface folds at the level of the Z-lines. Plasma membrane intramembrane particles were randomly distributed and showed the same numerical density on the E-faces of both isolated and intact-heart myocytes. However, P-face particle density was slightly reduced in the isolated cells. It is concluded that the few differences detected in the isolated cells do not reflect any fundamental derangement of their properties.

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↗