Time Course of Ouabain Uptake in Isolated Myocardial Cells: Dependence on Extracellular Potassium and Calcium Concentration

Meldgaard, L.; Steiness, Eva; Waldorff, S

doi:10.1111/j.1476-5381.1981.tb10427.x

Cited by 10 publications

(6 citation statements)

References 18 publications

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“…Low S K levels affect myocardial resting membrane potential, which increases the probability of ventricular arrhythmias and sudden cardiac death (11). Hypokalemia can also predispose patients to developing diastolic dysfunction, digoxin toxicity, and insulin resistance, all of which increase the risk for cardiovascular events and death (12)(13)(14)(15)(16). Dietary potassium depletion has been linked to the genesis of hypertension, and supplementation can improve BP control (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

Serum Potassium and Outcomes in CKD

Korgaonkar¹,

Tilea²,

Gillespie³

et al. 2010

Clinical Journal of the American Society of Nephrology

197

159

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Background and objectives:The relationship between serum potassium (S K ) and mortality in chronic kidney disease (CKD) has not been systematically investigated.Design, setting, participants, & measurements: We examined the predictors and mortality association of S K in the Renal Research Institute CKD Study cohort, wherein 820 patients with CKD were prospectively followed at four US centers for an average of 2.6 years. Predictors of S K were investigated using linear and repeated measures regression models. Associations between S K and mortality, the outcomes of ESRD, and cardiovascular events in time-dependent Cox models were examined.Results: The mean age was 60.5 years, 80% were white, 90% had hypertension, 36% had diabetes, the average estimated GFR was 25.4 ml/min per 1.73 m 2 , and mean baseline S K was 4.6 mmol/L. Higher S K was associated with male gender, lower estimated GFR and serum bicarbonate, absence of diuretic and calcium channel blocker use, diabetes, and use of angiotensinconverting enzyme inhibitors and/or statins. A U-shaped relationship between S K and mortality was observed, with mortality risk significantly greater at S K <4.0 mmol/L compared with 4.0 to 5.5 mmol/L. Risk for ESRD was elevated at S K <4 mmol/L in S K categorical models. Only the composite of cardiovascular events or death as an outcome was associated with higher S K (>5.5).Conclusions: Although clinical practice usually emphasizes greater attention to elevated S K in the setting of CKD, our results suggest that patients who have CKD and low or even low-normal S K are at higher risk for dying than those with mild to moderate hyperkalemia.

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Section: Discussionmentioning

confidence: 99%

Serum Potassium and Outcomes in CKD

Korgaonkar¹,

Tilea²,

Gillespie³

et al. 2010

Clinical Journal of the American Society of Nephrology

197

159

View full text Add to dashboard Cite

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“…It shortened in excess Ca and K-containing solution. An is known that Ca activates the neuronal Na,K-ATPase unexpected observation was made in the rabbit pul- , decreases internal Na activity monary artery, namely that excess K failed to antagalready elevated by Na-pump inhibition (Deitmer & (Meldgaard et al, 1981) and further delays the tion, the cardiac glycoside was applied together with ouabain-evoked rise of the miniature endplate poten-excess Ca (Figure 4). The rate of release did not differ tial (Baker & Crawford, 1975).…”

Section: Discussionmentioning

confidence: 99%

“…Baker & Crawford (1975) have shown that external Ca removal shortens the initial delay of ouabain-evoked acetylcholine release from the motor nerve terminal. In Na-pump inhibited Purkinje fibres, excess Ca decreased the internal Na activity (Deitmer & Ellis, 1978) and in myocardial cells excess Ca inhibited both the binding and uptake of ouabain (Meldgaard et al, 1981). Furthermore Powis et al (1983) have shown that Ca stimulates the neuronal Na,K-ATPase.…”

Section: Introductionmentioning

confidence: 99%

The action of excess potassium and calcium on ouabain‐evoked [³H]‐noradrenaline release from the rabbit pulmonary artery

Magyar¹,

Nguyen²,

Török³

et al. 1986

British J Pharmacology

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[3H]‐noradrenaline ([3H]‐NA) release from the main pulmonary artery of the rabbit has been measured in the presence of neuronal (cocaine, 3 × 10−5 M) and extraneuronal (corticosterone, 5 × 10−5 M) uptake blockers. Removal of K from the external medium increased the [3H]‐NA release. In the absence of external K, ouabain (10−4 M) further enhanced the neurotransmitter release. The ‘K‐free’ stimulated [3H]‐NA release was inhibited by an increase of external Ca (7.5 mM), an action antagonized by ouabain. After preperfusion of the preparations for 30 min with either excess K (23.6 mM) or excess Ca (7.5 mM), the ouabain‐stimulated [3H]‐NA release was inhibited by about 50%; the rates of inhibition did not differ significantly from each other. However, the characteristic initial delay before ouabain‐evoked neurotransmitter release was shortened in excess K, and prolonged in excess Ca‐containing solution. When both excess K and Ca were applied together 30 min before ouabain perfusion, the action of ouabain in releasing neurotransmitter was also inhibited but the rate of inhibition did not differ significantly from that seen when K or Ca were applied separately. The action of K in shortening the initial delay was partly antagonized by Ca. Excess Ca antagonized the inhibition of ouabain‐stimulated [3H]‐NA release caused by excess K when Ca and ouabain were applied together after 30 min preperfusion with excess K‐containing solution. Again excess Ca failed to inhibit the ouabain‐evoked neurotransmitter release if ouabain and excess K were applied together after excess Ca preperfusion (30 min). In both cases the initial delay of ouabain action was greatly shortened. The results suggest a Na‐Ca competition at the external activation site of the nerve terminal sodium‐pump similar to that of Na‐K competition. Furthermore it seems that there is a sort of K‐Ca competition as well, suggested by the finding that excess Ca prevented the inhibition caused by excess K of ouabain‐evoked noradrenaline release and vice versa.

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“…Experiments carried out in the 1970s and 1980s demonstrated that hypokalemia enhances digoxin toxicity by at least two mechanisms: increased cardiac glycoside binding to Na ϩ -K ϩ -ATPase, and reduced renal clearance of digitalis glycosides due to increased proximal tubule reabsorption [17][18][19].…”

Section: How Do Abnormal Serum Potassium Levels Affect the Toxicity Omentioning

confidence: 99%

Case files of the medical toxicology fellowship of the California poison control system—San Francisco: Calcium plus digoxin—More taboo than toxic?

Erickson

Olson

2008

J. Med. Toxicol.

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What are the effects of elevated potassium on the heart? As in other tissues, most sodium in the myocardium is extracellular, and most potassium is intracellular. The concentrations of each are maintained by the Na ϩ -K ϩ -ATPase pump and are also dependent on the relative permeability of the cell surface to migration of Na ϩ or K ϩ down their respective concentration gradients. In a normal cardiac cell, the resting potential during diastole is approximately Ϫ90 mV. If Na ϩ enters the cell, the electrical potential becomes less negative; conversely, if K ϩ leaves the cell the transmembrane potential becomes more negative [1,2].Electrical signals are propagated through the heart by action potentials that open voltage-gated sodium channels, allowing rapid influx of Na ϩ and depolarization of the cell (phase 0), as depicted in Figure 1. The rate of rise of phase 0 is directly proportional to the number of sodium channels that are opened during depolarization. The more negative the resting membrane potential at the start of phase 0, the greater the number of Na ϩ channels in the "ready-to-open" state. Conversely, if the resting membrane potential is less negative than normal, fewer Na ϩ channels are ready to open and depolarization will be less robust, with reduced upstroke velocity (V max ), reduced action potential amplitude, and reduced conduction velocity.As the membrane potential reaches Ϫ40 to Ϫ45 mV during phase 0 depolarization, voltage-gated calcium channels are opened, allowing calcium entry. At about the same time, potassium channels open and allow potassium to exit the cell, balancing the influx of calcium. Together, the opposing effects of calcium influx

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Time Course of Ouabain Uptake in Isolated Myocardial Cells: Dependence on Extracellular Potassium and Calcium Concentration

Cited by 10 publications

References 18 publications

Serum Potassium and Outcomes in CKD

Serum Potassium and Outcomes in CKD

The action of excess potassium and calcium on ouabain‐evoked [³H]‐noradrenaline release from the rabbit pulmonary artery

Case files of the medical toxicology fellowship of the California poison control system—San Francisco: Calcium plus digoxin—More taboo than toxic?

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Time Course of Ouabain Uptake in Isolated Myocardial Cells: Dependence on Extracellular Potassium and Calcium Concentration

Cited by 10 publications

References 18 publications

Serum Potassium and Outcomes in CKD

Serum Potassium and Outcomes in CKD

The action of excess potassium and calcium on ouabain‐evoked [3H]‐noradrenaline release from the rabbit pulmonary artery

Case files of the medical toxicology fellowship of the California poison control system—San Francisco: Calcium plus digoxin—More taboo than toxic?

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The action of excess potassium and calcium on ouabain‐evoked [³H]‐noradrenaline release from the rabbit pulmonary artery