Potassium loss from rabbit myocardium during hypoxia: Evidence for passive efflux linked to anion extrusion

Gaspardone, Achille; Shine, Kenneth I.; Seabrooke, S.R.; Poole‐Wilson, Philip A.

doi:10.1016/s0022-2828(86)80902-6

Cited by 31 publications

(4 citation statements)

References 39 publications

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“…The lack of effect of tolbutamide or glibenclamide upon the action potential or upon the steady-state I-V relationship suggests that these channels are not significantly activated in the non-ischaemic state (it also indicates that tolbutamide does not affect other background K+ currents such as iKi). Finally, our experiments indicate that K+ accumulation is not linked obligatorily to the efflux of anions such as Clor lactate, in contrast to conclusions drawn in previous work (Gaspardone et al 1986). Although both anion and K+ efflux seem to occur during ischaemia, each flux must be via an independent pathway.…”

Section: Discussioncontrasting

confidence: 99%

“…The K+ efflux has been suggested to be linked to lactate efflux which also increases during ischaemia (Gaspardone et al 1986). Lactate efflux occurs to a large extent via a transmembrane carrier inhibitable by a-cyano-4-hydroxy-cinnamic acid (ocHC) (Halestrap & Denton, 1974;de Hemptinne, Marrannes & Vanheel, 1983).…”

Section: Effect Of Inhibiting Lactate Effluxmentioning

confidence: 99%

“…One possible mechanism is that K+ efflux requires the simultaneous efflux of an anion such as Clor lactate (Kleber, 1983; Gaspardone, Shine, Seabrooke & Poole-Wilson, 1986), perhaps via a co-transport carrier mechanism. An alternative possibility is that additional K+ channels open up during ischaemia, thus accelerating the passive diffusive leak of K+ from the cell (Vleugels, Vereeke & Carmeliet, 1980).…”

Section: Introductionmentioning

confidence: 99%

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Mechanism of potassium efflux and action potential shortening during ischaemia in isolated mammalian cardiac muscle.

Gasser

Vaughan‐Jones

1990

The Journal of Physiology

129

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SUMMARY1. Ischaemia was simulated in the isolated sheep cardiac Purkinje fibre and guinea-pig papillary muscle by immersing the preparations in paraffin oil. lonselective microelectrodes recorded potassium (K+) and pH (pH.) in the thin film of Tyrode solution trapped at the fibre surface while other microelectrodes recorded intracellular pH (pHi), membrane potential and action potentials (AP) (evoked by field stimulation), or membrane current (two-microelectrode voltage clamp in shortened Purkinje fibres). Twitch tension was also monitored. The paraffin oil model reproduced the salient characteristics of myocardial ischaemia, i.e. a decrease of twitch tension; a decrease of pHi and pHs; a rise in K+ (by 2-3 mM); a depolarization of diastolic membrane potential; considerable shortening of the AP (up to 30% within 4 min).2. The sulphonylurea compounds, glibenclamide (200 ,UM) and tolbutamide (1 mM), known inhibitors of the KATP channel, completely blocked the ischaemic rise of K+ and prevented AP shortening. Ischaemic tension decline was notably less pronounced in the presence of sulphonylureas.3. The ischaemic increase of slope conductance (Purkinje fibre) was prevented by 1 mM-tolbutamide and 200 ,tM-glibenclamide. 4. Sulphonylureas did not affect resting membrane potential, the AP or the current-voltage relationship under non-ischaemic conditions (this also indicates that ischaemic K+ accumulation is not fuelled by the background K+ current [iKJ] which was shown, as expected, to be Ba2' sensitive).5. In a normally perfused preparation, reducing intracellular ATP by inhibiting glycolysis with 2-deoxyglucose (DOG) produced a similar AP shortening plus a membrane hyperpolarization, both of which were inhibited by tolbutamide or glibenclamide. The AP shortening was not related uniquely to the fall of pHi observed under these conditions since experimentally reducing pHi (by reducing pH.in the absence of DOG) lengthened rather than shortened the AP.6. The possibility that the ischaemic rise in K+ might be the cause of AP shortening was excluded by the observation that, in a normally perfused Purkinje fibre, experimentally reducing pHi (by an amount similar to that seen during ischaemia) completely neutralized the AP-shortening effect of an elevated K+ (from MS 8314 R. N. A. GASSER AND R. D. VA UGHAN-JONES 4-5 to 6-5 mM). Furthermore, the sulphonylurea-sensitive AP shortening seen during DOG treatment (paragraph 5) could not have been associated with a K' rise since, in these particular experiments, the fibres were well perfused and diastolic membrane potential hyperpolarized.7. Ischaemic K+ accumulation was not affected by (i) the inhibitor of lactate transport, cc-cyano-4-hydroxycinnamic acid (4 mM), (ii) a very high concentration of bumetanide (2 mM: a known high-affinity inhibitor of Na+-K+-2Cl-co-transport), and (iii) total Cl-removal. This indicates that ischaemic K+ efflux is not linked with anion movement.8. We conclude that simulated ischaemia leads to K+ accumulation through opening of sulphonylurea-sens...

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Section: Discussioncontrasting

confidence: 99%

Section: Effect Of Inhibiting Lactate Effluxmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mechanism of potassium efflux and action potential shortening during ischaemia in isolated mammalian cardiac muscle.

Gasser

Vaughan‐Jones

1990

The Journal of Physiology

129

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“…Our study does not give more insight into the cause of the ischemia-induced rise of [K+]our Several hypotheses have been put forward in recent years to explain the exact mechanism for the loss of potassium from ischemic or hypoxic myocardium, but until now there is no consensus. The potassium loss has been attributed to inhibition of membrane-bound Na+-K ÷-ATPase [15,16], a selective increase in membrane conductance to K ÷ ions [17], passive cotransport to efflux of anions [18,19], acidosis, or H÷-K + exchange [20][21][22]. ATP-regulated potassium channels may also provide an alternative explanation for the increased K ÷ conductance [23][24][25].…”

Section: Discussionmentioning

confidence: 99%

The effects of calcium antagonists on extracellular potassium accumulation during global ischaemia in isolated perfused rat hearts

Heijnis

Coronel

Zwieten

1991

Cardiovasc Drug Ther

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The effects of equipotent concentrations of diltiazem, verapamil, and nifedipine upon the accumulation of extracellular potassium [K+]out and the left ventricular pressure (LVP) were studied during global ischemia in isolated perfused rat hearts. Measurement of [K+]out and LVP were performed in two series of experiments. Diltiazem (2 x 10(-6), 3 x 10(-6), and 10(-5) M), verapamil (3 x 10(-8), 10(-7), and 3 x 10(-7) M), and nifedipine (3 x 10(-8), 10(-7), and 1.5 x 10(-7) M) were able to slow, in a concentration-dependent manner, the initial rate of rise of [K+]out without affecting the final plateau value of [K+]out reached at t = 5 to t = 10 minutes. Notably, at the lowest concentrations, which slightly influenced LVP diltiazem, verapamil, and to a lesser degree nifedipine, were still able to slow the rise in [K+]out. In addition, after preperfusion with low-calcium media [( Ca2+] from 1.8 to 1.3 or 0.9 mM), inducing similar negative inotropic effects as those of the calcium antagonists, the rise in [K+]out was not significantly influenced. Our data indicate that the ability to slow the rise in [K+]out is a specific characteristic of calcium antagonists that is independent of their negative inotropic effects.

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Ion Movements Early in Myocardial Ischaemia: Relation to Arrhythmias, Early Contractile Failure and Tissue Necrosis

Poole‐Wilson¹

1992

Myocardial Response to Acute Injury

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Potassium loss from rabbit myocardium during hypoxia: Evidence for passive efflux linked to anion extrusion

Cited by 31 publications

References 39 publications

Mechanism of potassium efflux and action potential shortening during ischaemia in isolated mammalian cardiac muscle.

Mechanism of potassium efflux and action potential shortening during ischaemia in isolated mammalian cardiac muscle.

The effects of calcium antagonists on extracellular potassium accumulation during global ischaemia in isolated perfused rat hearts

Ion Movements Early in Myocardial Ischaemia: Relation to Arrhythmias, Early Contractile Failure and Tissue Necrosis

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