Effects of strophanthidin upon contraction and ionic exchange in rabbit ventricular myocardium: Relation to control of active state

189

SUMMARY1. The effects of ouabain on the electrical coupling between cells and the conduction velocity, 0, were studied in ventricular muscle preparations from calf and cow hearts using a silicon-oil-chamber.2. After 90 min of exposure to 2 x 106 M ouabain, an increase of the inside longitudinal resistance, Rl, from 420Q cm to 1032 Q cm was observed. Assuming a constant myoplasmic resistivity this presumably reflects a reduced electrical coupling between myocardial cells.3. Concomitantly, 0 was decreased from 50 3 to 29-4 cm/sec. This change could be explained by the observed alterations in the maximal rate of rise of the action potential, (d V/dt) max, the amplitude of the action potential, Vp, the membrane capacity Cf, and the sum, respectively, of the inside and outside longitudinal resistance per unit distance (rj + ro). Quantitatively, about 60 % of the decrease of 0 could be accounted for by the experimentally determined increase of Ri.4. Time course studies revealed a biphasic action of ouabain on Ri. An early dose-dependent drop in Ri, equivalent to an improvement of the intercellular coupling, was followed by a delayed massive increase in Ri, whose onset and magnitude were also concentration-dependent.5. The delayed increase in Ri was associated with an increase of the diastolic tension. Toxic ouabain doses (2 x 10-6M) produced irreversible changes on both parameters, whereas therapeutic doses (< 5 X 10-7 M) affected neither of them.

“…6). (Langer & Serena, 1970). Thus, relatively little change in myoplasmic conductivity would be expected.…”

Section: Intercellular Coupling and Ouabain Comparison Ofmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The actions of ouabain on intercellular coupling and conduction velocity in mammalian ventricular muscle.

Weingart¹

1977

189

“…), would produce no increase in the internal Na activity. Thus the suggestion that ouabain produces an increase of contractility by inhibition of the Na pump and subsequent increase of the [Ca]i via a Na/Ca exchange process (Baker et al 1969;Langer & Serena, 1970) cannot completely account for its action as concentrations of ouabain less than 10-7 M reversibly increase the contractility of sheep heart Purkinje fibres (Blood, 1975). The irreversible effects on contractility of the glycoside could be accounted for by the almost irreversible increases in the internal Na activity, perhaps by increasing the [Ca2+], via a Na/Ca exchange across the cell membrane.…”

Section: The Effects Of [K]0 and Ouabainmentioning

confidence: 99%

The effects of external cations and ouabain on the intracellular sodium activity of sheep heart Purkinje fibres

Ellis¹

1977

313

219

SUMMARY1. The intracellular Na activity of sheep heart Purkinje fibres has been measured using recessed-tip Na+-sensitive glass micro-electrodes.2. The internal Na activity was 7-2 + 2-0 mm (mean + S.D., n = 32) at the normal external Na concentration, [Na]0, in these experiments of 140 mm (equivalent to an external Na activity of 105 mM). The equilibrium potential for Na across the fibre membrane was therefore approximately + 70 mV. 4. The removal of external K produced an easily reversible increase in the internal Na with an initial rate equivalent to a concentration change of 0-24 + 0 07 m-mole/min (mean + S.D., n = 8).5. Ouabain produced increases in the internal Na activity that were only very slowly reversible. The threshold concentration for producing an increase was approximately 10-7 M. 10. The relationship between internal Na and contractility is discussed.

“…The resulting rise of intracellular Ca is thought to allow the sarcoplasmic reticulum to increase its amount of stored Ca, so that it can release more Ca with each action potential, to cause an increase in the force of contraction. Langer & Serena (1970) investigated the positive inotropic effect of the cardiotonic steroid strophanthidin on heart muscle. As Schatzmann (1953) had already shown that this group of drugs inhibit the Na-K pump of red blood cells, Langer & Serena (1970) proposed that cardiotonic steroids make the heart beat more strongly by inhibiting the Na-K pump of heart muscle cells, to cause a rise of aNa.…”

Section: Introductionmentioning

confidence: 99%

Dissociation between force and intracellular sodium activity with strophanthidin in isolated sheep Purkinje fibres.

Boyett¹,

Hart²,

Levi³

1986

SUMMARY1. We have recorded membrane potential, intracellular Na activity (aika) and force of contraction in sheep Purkinje fibres. Force and aia were recorded continuously and simultaneously during exposure to strophanthidin and its subsequent washing off.2. Exposure to strophanthidin in concentrations of 1-5 x 10-7, 5 x 10-7 and 10-5 M caused an increase in force of contraction which was temporally dissociated from the increase of aba.3. There was hysteresis in the relationship between force and aia when the period of increasing force was compared to the period of decreasing force. When force increased on exposure to strophanthidin, the same aka was always associated with a higher force than when force was decreasing while washing off the drug.4. For the same rise of aa higher doses of strophanthidin produced larger rises of force than lower doses.5. When diphenylhydantoin was present in the bathing solution at concentrations of 10-5 and 10-4 M, the relation between force and aia with 10-5 M-strophanthidin had a less steep slope, but still displayed hysteresis.6. The relationship between force and aka during changes of the bathing K concentration also displayed a hysteresis, which was in the same direction as that found with strophanthidin.7. These results are discussed in relation to proposed mechanisms of action of strophanthidin and more generally in relation to the factors linking force of contraction and aNa. We conclude that in sheep Purkinje fibres the increase of force caused by strophanthidin is not solely due to an increase of a, and that other interventions can also result in hysteresis between force and aNa.