Evidence for electrogenic Na+ pumping in human atrial myocardium

Rasmussen, Helge H.; TenEick, R. E.; McCullough, Judith; Singer, Donald H.

doi:10.1016/s0022-2828(84)80660-4

Cited by 7 publications

(5 citation statements)

References 9 publications

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“…The activation of the electrogenic Na pump current may be secondary to a rise in intracellular Na + concentration due to Na+ influx via TTX-sensitive or background leak channels. Recently, RASMUSSEN et al (1984) reported that an electrogenic Na pump current contributed to the maintenance of the resting potentials in human atria.…”

Section: Discussionmentioning

confidence: 99%

“…It is suggested that the low resting potentials of diseased atrial fibers may be due to decreases in membrane K + conductance (TRAUTWEIN et al, 1962;TEN EICK and SINGER, 1979). On-the other hand, there are possibilities that increases in permeability to ions such as Na+, Cat+, and Cl-, as well as impairment of the electrogenic Na + pump might also contribute to the partial depolarization of the diseased human atrium (RASMUSSEN et al, 1984). Recently, LEE (1986) reported that sarcolemmal Na, K-ATPase activity was significantly low in diseased human atrial tissues compared with normal ones.…”

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confidence: 99%

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Factors related to the low resting membrane potentials of diseased human atrial muscles.

Imanishi

Arita

1987

Jpn.J.Physiol

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we studied the ionic mechanism of low resting potential (RP) of quiescent "diseased" human atrial fibers. The RP was -49.7 ± 0.8 mV (n= 179) in normal Tyrode's solution (5.4 mM [K]0, 36°C). The changes in RP measured at various levels of [K]0 appeared to fit the RP-[K]0 relationship predicted by the Goldman-Hodgkin-Katz equation, assuming PNa/PK ratio (a) to be 0.102 and [K]; to be 131.9 mM. The a far exceeded the normal value (about 0.01) by a factor of 10. Acetylcholine (ACh, 10 /1M) led to marked increases in the RP. An application of tetrodotoxin (TTX, 6 jiM) and perfusion with low [Na]o (10% of the control) media in the presence and absence of ACh produced considerable hyperpolarizations of the RP. These' findings indicate that increased a value is due to a combination of decreased PK and increased PNa. Applications of ouabain (5 µM) and a cooling procedure (12.3°C) depolarized the membrane, whereas epinephrine (1 µM) hyperpolarized it. Transient hyperpolarization, which exceeded the steady state levels of RP at 5.4 mM [K]0, was observed with perfusing of 5.4 mM [K]0 media following perfusion with K-free media. These findings suggest that electrogenic Na pump current plays a significant role in the maintenance of the RP. In conclusion, partial depolarization of "diseased" human atrial fibers was attributed to both decreases in membrane K + conductance and increases in Na + conductance. The electrogenic outward pump current seemed to protect the fibers from severe depolarization produced by the conductance abnormality (increased PNa/PK)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Factors related to the low resting membrane potentials of diseased human atrial muscles.

Imanishi

Arita

1987

Jpn.J.Physiol

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“…On the other hand, an increase in [K]0 up to 20mm drastically reduced the hyperpolarization produced by Iso but it would not be expected to block electrogenic Na+ pumping. It should be pointed out that, under no circumstances, did the catecholamine hyperpolarization reach a value more negative than the calculated equilibrium potential for K+ (EK); this also argues against a participation of an electrogenic Na+ pump (Rasmussen et al, 1984;1986). In isolated myocardial cells from the guinea-pig, it has been shown that depolarization by 20 mm [K]0 does not reduce electrogenic pumping (Gadsby et al, 1985).…”

Section: Discussionmentioning

confidence: 97%

Analysis of the hyperpolarizing effect of catecholamines on canine cardiac Purkinje fibres

Neto

Sperelakis

1989

British J Pharmacology

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The hyperpolarization induced by catecholamines on barium‐depolarized (0.2–0.8 mm BaCl) canine cardiac Purkinje fibres, in vitro, was studied by use of conventional microelectrode recordings of transmembrane electrical potentials. Noradrenaline, adrenaline and isoprenaline hyperpolarized Purkinje fibres in a concentration‐dependent manner from a threshold concentration around 5 nm. The three catecholamines were shown to be approximately equipotent. Tachyphylaxis was observed when the interval between catecholamine applications was less than 15 min. Atenolol (10 μm) blocked the hyperpolarization reversibly and theophylline (0.5 mm) potentiated it. Tetrodotoxin (5 μm) did not affect the hyperpolarization induced by isoprenaline. Acetylcholine and histamine, up to 10 μm, were not effective in hyperpolarizing Purkinje fibres. Low extracellular potassium concentrations (zero and 1 mm) did not affect the hyperpolarization, but high extracellular potassium concentrations (10–20 mm), markedly reduced the effect of isoprenaline (100 nm). Reduction of the extracellular sodium concentration produced a roughly proportional reduction in the isoprenaline‐induced hyperpolarization. The hyperpolarization was reversibly blocked in 34 mm sodium Tris‐Tyrode solution. The hyperpolarization was not reduced in Tyrode solution containing 0.6 mm calcium, but was drastically reduced in zero‐calcium Tyrode solution. This effect was reversible. Addition of verapamil (5–10 μm) diminished the hyperpolarization, in a concentration‐dependent manner. This effect was partially reversed after washing. Ouabain (0.7–1 μm) significantly reduced the isoprenaline‐induced hyperpolarization, but 2,4‐dinitrophenol (0.2 mm) did not affect it. Caesium chloride (20 mm) abolished the hyperpolarization. The blockade was only partially reversed upon washing. It is suggested that the hyperpolarization induced by a short exposure to catecholamines is mainly due to an increase in potassium permeability (PK). A mechanism involving calcium‐dependent potassium channels might underlie the increase in PK.

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“…Significant findings include: (Sakmann and Trube, 1984); a shift in the reversal potential; and a change in the voltage-dependence of rectification (see Lu, 2004 for a review). ii The resting potential is also modulated by the atrial Na + /K + pump current (Rasmussen et al, 1984(Rasmussen et al, , 1986Workman et al, 2003), which is highly sensitive to [K + ] o and [Na + ] i . iii Although hyperkalemic increases above 5 mM are known to strongly depolarize V r , very few studies in human atrium have investigated this effect at [K + ] o levels in the hypokalemic range.…”

Section: Electrophysiology Of Human Atrial Myocytesmentioning

confidence: 99%

“…The resting potential is also modulated by the atrial Na + /K + pump current ( Rasmussen et al, 1984 , 1986 ; Workman et al, 2003 ), which is highly sensitive to [K + ] o and [Na + ] i .…”

Section: Introductionmentioning

confidence: 99%

Immediate and Delayed Response of Simulated Human Atrial Myocytes to Clinically-Relevant Hypokalemia

et al. 2021

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Although plasma electrolyte levels are quickly and precisely regulated in the mammalian cardiovascular system, even small transient changes in K+, Na+, Ca2+, and/or Mg2+ can significantly alter physiological responses in the heart, blood vessels, and intrinsic (intracardiac) autonomic nervous system. We have used mathematical models of the human atrial action potential (AP) to explore the electrophysiological mechanisms that underlie changes in resting potential (Vr) and the AP following decreases in plasma K+, [K+]o, that were selected to mimic clinical hypokalemia. Such changes may be associated with arrhythmias and are commonly encountered in patients (i) in therapy for hypertension and heart failure; (ii) undergoing renal dialysis; (iii) with any disease with acid-base imbalance; or (iv) post-operatively. Our study emphasizes clinically-relevant hypokalemic conditions, corresponding to [K+]o reductions of approximately 1.5 mM from the normal value of 4 to 4.5 mM. We show how the resulting electrophysiological responses in human atrial myocytes progress within two distinct time frames:(i) Immediately after [K+]o is reduced, the K+-sensing mechanism of the background inward rectifier current (IK1) responds. Specifically, its highly non-linear current-voltage relationship changes significantly as judged by the voltage dependence of its region of outward current. This rapidly alters, and sometimes even depolarizes, Vr and can also markedly prolong the final repolarization phase of the AP, thus modulating excitability and refractoriness.(ii) A second much slower electrophysiological response (developing 5–10 minutes after [K+]o is reduced) results from alterations in the intracellular electrolyte balance. A progressive shift in intracellular [Na+]i causes a change in the outward electrogenic current generated by the Na+/K+ pump, thereby modifying Vr and AP repolarization and changing the human atrial electrophysiological substrate.In this study, these two effects were investigated quantitatively, using seven published models of the human atrial AP. This highlighted the important role of IK1 rectification when analyzing both the mechanisms by which [K+]o regulates Vr and how the AP waveform may contribute to “trigger” mechanisms within the proarrhythmic substrate. Our simulations complement and extend previous studies aimed at understanding key factors by which decreases in [K+]o can produce effects that are known to promote atrial arrhythmias in human hearts.

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Evidence for electrogenic Na+ pumping in human atrial myocardium

Cited by 7 publications

References 9 publications

Factors related to the low resting membrane potentials of diseased human atrial muscles.

Factors related to the low resting membrane potentials of diseased human atrial muscles.

Analysis of the hyperpolarizing effect of catecholamines on canine cardiac Purkinje fibres

Immediate and Delayed Response of Simulated Human Atrial Myocytes to Clinically-Relevant Hypokalemia

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