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Biomedical subjects

C H Fry

Publications and source records attributed to C H Fry.

At least 91 records · Page 5Linked to original sources

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↗

Measurement and control of intracellular magnesium ion concentration in guinea pig and ferret ventricular myocardium.

Intracellular magnesium and sodium ionic concentrations have been measured in mammalian ventricular myocardium using ion-selective micro-electrodes. The values for [Na+]i and [Mg2+]i are 9.5 +/- 0.3 and 2.4 +/- 0.2 mM, respectively. Increasing extracellular [Mg] or decreasing extracellular [Na] both caused a rise of [Mg2+]i and a fall of [Na+]i. Superfusion with ouabain caused a small rise of [Mg2+]i as well as a rise of [Na+]i. Reduction of extracellular [Mg] or cell depolarisation had no effect on [Mg2+]i. A possible hypothesis to explain these results is proposed, namely that the transmembrane Na+ and Mg2+ gradients are coupled such that an alteration of one gradient will affect the other. However, the relative stability of [Mg2+]i suggests that it is also affected by other factors, such as intracellular buffering of the ion.

Animals↗

Net calcium exchange in adult rat ventricular myocytes: an assessment of mitochondrial calcium accumulating capacity.

Net calcium exchange has been measured in a suspension of cardiac myocytes after treatment with digitonin. The exchange is believed to be across the mitochondrial membranes and can be stimulated or inhibited by agents augmenting or blocking mitochondrial electron transport. The uptake of calcium shows a strong dependence on suspension pCa but is not evident below 1 microM (pCa 6.0). It is suggested that the net calcium exchange is a balance of the two processes which are equivalent at pCa 6.0. The measurement of mitochondrial specific activity for calcium uptake allows a calculation of the rapidity with which the cardiac mitochondria would affect sarcoplasmic calcium after a sudden rise. It is suggested that the organelle could partly affect relaxation especially at the peak of contraction.

Animals↗

The effects of sodium, hydrogen and magnesium ions on mitochondrial calcium sequestration in adult rat ventricular myocytes.

The effect of Na+, H+ and Mg2+ ions on net calcium exchange induced in digitonin-treated myocytes has been investigated. Raising the [Na] from 1.4 to 31.4 mM revealed a sodium-sensitive fraction of net calcium exchange with a K1/2 for Na+ ions of 12 mM, alongside the respiration-dependent accumulation of calcium. An acidosis, but not an alkalosis, was found to depress both of these processes. Mg2+ ions exerted an effect solely on the respiration-dependent calcium sequestration. A simple semi-empirical model based on the experimental data was formulated to assess the effects that altering sarcoplasmic [Na+] and [H+] would have on the calcium-handling properties of cardiac mitochondria. It is concluded that part of the inotropic effects of these ions could be mediated via this organelle.

Animals↗

Inotropic and vasodilator effects of amrinone on isolated human tissue.

The effects of amrinone on human umbilical artery and human myocardium were studied. Amrinone produced dose related increases in tension, dT/dtmax and dT/dtmin in myocardium from patients who were NYHA grade I (n = 1) and II (n = 4). The responses to amrinone of these tissues were similar to the response seen in normal guinea-pig myocardium (n = 34). The drug had no inotropic effect on tissue from NYHA grade III patients (n = 5). The inotropic response of the tissues to amrinone was inversely related to length of history and severity of heart failure in the patients from whom the tissues were obtained. Amrinone caused dose related relaxation of the human umbilical artery. The vasodilator properties, but not the positive inotropic effects of amrinone were detectable at concentrations of the drug obtained during oral therapy (0.4 to 4.0 micrograms X ml-1). These findings support the view that in patients with congestive cardiac failure amrinone acts by vasodilatation with no clinically important positive inotropic effect.

Aminopyridines↗

A new in vitro microsuperfusion technique for investigation of human detrusor muscle.

There is a paucity of information regarding the behaviour of human detrusor muscle in vitro. This is mainly due to the dependence of muscle bath techniques on large strips of material, which can be obtained only at open operations and which may not be viable because of limited diffusion of oxygen and metabolites through the tissue. We report a new technique for the in vitro study of muscle obtained during endoscopic procedures by cup biopsy. The results obtained from normal muscle show that this technique gives consistent and reproducible results.

Atropine↗

Effects of acid-base changes on excitation--contraction coupling in guinea-pig and rabbit cardiac ventricular muscle.

1. Respiratory and metabolic acid-base changes caused similar steady-state changes in the contractility of cardiac ventricular muscle, but the rate of response was more rapid with the former intervention. 2. Variations in extracellular pCO2 and [HCO3-] at constant pH caused only a transient change in contractility. 3. An intracellular pH change can describe the above events. 4. The changes in contractility caused by extracellular acid-base changes could be explained by competition between Ca2+ and H+ ions for a single process. 5. Assuming an electroneutral scheme whereby one extracellular Ca2+ ion or two intracellular H+ ions compete for a binding site, the interior of ventricular cells must be better buffered than the extracellular fluid. 6. H+ ions evoked a release of Ca2+ ions from a mitochondrial suspension with a time course similar to the partial recovery of tension observed during a respiratory acidosis. 7. Respiratory and metabolic acidosis depressed the action potential plateau and prolonged repolarization. 8. The resting potential and the maximum rate of depolarization were unaffected by the above acid-base changes. 9. An acidosis depressed Ca2+ influx through the slow inward channel by an amount sufficient to account for the observed contractility changes. 10. It is concluded that between pH 7.6 and 6.6 the major physiological effect of an acidosis is to depress the slow inward current as a result of an intracellular pH change.

Acid-Base Equilibrium↗

Effect of ouabain in therapeutic concentrations on K+ exchange and contraction of human and rabbit myocardium.

1. Experiments were undertakn on strips of human atrial and ventricular muscle, on right ventricular rabbit papillary muscles and on the rabbit interventricular septum. 2. In all preparations an increase of developed tension after 30 min exposure to ouabain was apparent only at or above a concentration of 10(-7) mol/l (73 micrograms/l). 3. In the rabbit septum there was a net loss of potassium on exposure to ouabain if the concentration was greater than 10(-7) mol/l. There was no net loss, or gain, of potassium at lower concentrations. Loss of potassium, indicating inhibition of the sodium pump, could not be dissociated from the positive inotropic effect of ouabain. 4. The greater sensitivity to ouabain of human myocardium in vivo (10(-8) mol/l) than in vitro (10(-7) mol/l) may be due to cellular changes occurring in isolated preparations.

Action Potentials↗

Acute effects of diuretics on potassium exchange, mechanical function and the action potential in rabbit myocardium.

1. We have studied the acute effects of frusemide, triamterene and amiloride on potassium exchange, the action potential and mechanical function of isolated rabbit myocardium. 2. Potassium exchange in the myocardium was unaltered by these diuretics. 3. Frusemide and amiloride did not affect the action potential of rabbit papillary muscles. Triamterene caused a transient shortening of the action potential. 4. Frusemide and triamterene did not alter myocardial mechanical function in rabbit papillary muscles or the interventricular septum. Amiloride caused a reduction of about 5% in developed tension in two out of three papillary muscles.

Action Potentials↗

An analysis of the cable properties of frog ventricular myocardium.

1. The passive and active electrical parameters of frog ventricular myocardium have been measured. 2. The cytoplasmic resistivity has been determined by following changes in the resistance of a micro-electrode on penetration of a cell. 3. Unidimensional cable analysis using direct and alternating currents revealed the presence of a single time constant attributed to the surface membrane. 4. Longitudinal impedance measurements indicate that a second time constant is present in the intracellular pathway. 5. The results indicate that the resistance between cells is low so that action potentials can propagate from cell to cell by local circuits. 6. A three-dimensional cable analysis has also been carried out and compared to a simplified mathematical model which is presented in an Appendix and which closely approximates the experimental situation.

Action Potentials↗

Relationship between internal calcium and outward current in mammalian ventricular muscle; a mechanism for the control of the action potential duration?

In sheep and calf ventricular bundles, increasing the internal calcium by increasing the frequency of voltage-clamping to plateau range potentials increased the time-independent outward current. This effect was more marked with higher [Ca]o, and was reduced if the Ca current blockers Verapamil or D 600 were used. 2. If the internal Ca was increased by the addition of cyanide and reduction of external sodium the outward current was also increased. The frequency-dependent increase in outward current also occurred in this Na-poor (12 mM) solution. 3. Tension measurement on the ventricular bundles showed that a Na-free solution with cyanide did not cause a contracture. On changing from Tyrode to a Na-free solution containing cyanide, and on changing back to Tyrode there was a potentiation of the twitch. 4. In Na-poor solution with cyanide, although no contracture was found, ECa was less positive, suggesting that under these circumstances Ca accumulates at the inner side of the membrane, but not around the myofibrils. 5. The prolongation of the action potential in Cl-free solution is frequency-dependent. A greater prolongation is seen at lower frequencies suggesting that Cl current is relatively more important for repolarization at lower frequencies of stimulation. 6. It is suggested that calcium at the inner side of the membrane sets the level of the background outward current. A feed-back mechanism on this basis is proposed for the control of the action potential duration. Various factors that could influence this basic mechanism are discussed.

Action Potentials↗