Activation of the electrogenic sodium pump in guinea‐pig atria by external potassium ions

Glitsch, H. G.; Grabowski, Władysław; Thielen, J.

doi:10.1113/jphysiol.1978.sp012250

Cited by 50 publications

(16 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High [K + ] o stimulates the activity of the Na + -K + pump [33,82] and decreases a i Na [5]. Therefore, high [K + ] o opposes digitalis intoxication by decreasing DD slope and the rate by decreasing V os [63], as expected from a decreased Ca 2+ overload.…”

Section: Role Of Na + In Electrical Toxicitymentioning

confidence: 86%

Calcium Overload and Cardiac Function

Vassalle

Chen

2004

J Biomed Sci

View full text Add to dashboard Cite

The changes in cardiac function caused by calcium overload are reviewed. Intracellular Ca²⁺ may increase in different structures [e.g. sarcoplasmic reticulum (SR), cytoplasm and mitochondria] to an excessive level which induces electrical and mechanical abnormalities in cardiac tissues. The electrical manifestations of Ca²⁺ overload include arrhythmias caused by oscillatory (V_os) and non-oscillatory (V_ex) potentials. The mechanical manifestations include a decrease in force of contraction, contracture and aftercontractions. The underlying mechanisms involve a role of Na⁺ in electrical abnormalities as a charge carrier in the Na⁺-Ca²⁺ exchange and a role of Ca²⁺ in mechanical toxicity. Ca²⁺ overload may be induced by an increase in [Na⁺]_i through the inhibition of the Na⁺-K⁺ pump (e.g. toxic concentrations of digitalis) or by an increase in Ca²⁺ load (e.g. catecholamines). The Ca²⁺ overload is enhanced by fast rates. Purkinje fibers are more susceptible to Ca²⁺ overload than myocardial fibers, possibly because of their greater Na⁺ load. If the SR is predominantly Ca²⁺ overloaded, V_os and fast discharge are induced through an oscillatory release of Ca²⁺ in diastole from the SR; if the cytoplasm is Ca²⁺ overloaded, the non-oscillatory V_ex tail is induced at negative potentials. The decrease in contractile force by Ca²⁺ overload appears to be associated with a decrease in high energy phosphates, since it is enhanced by metabolic inhibitors and reduced by metabolic substrates. The ionic currents I_os and I_ex underlie V_os and V_ex, respectively, both being due to an electrogenic extrusion of Ca²⁺ through the Na⁺-Ca²⁺ exchange. I_os is an oscillatory current due to an oscillatory release of Ca²⁺ in early diastole from the Ca²⁺-overloaded SR, and I_ex is a non-oscillatory current due to the extrusion of Ca²⁺ from the Ca²⁺-overloaded cytoplasm. I_os and I_ex can be present singly or simultaneously. An increase in [Ca²⁺]_i appears to be involved in the short- and long-term compensatory mechanisms that tend to maintain cardiac output in physiological and pathological conditions. Eventually, [Ca²⁺]_i may increase to overload levels and contribute to cardiac failure. Experimental evidence suggests that clinical concentrations of digitalis increase force in Ca²⁺-overloaded cardiac cells by decreasing the inhibition of the Na⁺-K⁺ pump by Ca²⁺, thereby leading to a reduction in Ca²⁺ overload and to an increase in force of contraction.

show abstract

Section: Role Of Na + In Electrical Toxicitymentioning

confidence: 86%

Calcium Overload and Cardiac Function

Vassalle

Chen

2004

J Biomed Sci

View full text Add to dashboard Cite

show abstract

“…1B). Alternatively, addition of monensin at concentrations up to 10lM had no significant effect on TPP+ accumulation by cells in high K+ 20 MM monensin induced 20-30 mV hyperpolarization (interior negative). On the other hand, the time course of the monensin-induced hyperpolarization measured electrophysiologically was considerably faster than that observed by TPP+ distribution (i.e., t1/2 = 50 ± 10 sec electrophysiologically versus 5 min with TPP+-see Fig.…”

mentioning

confidence: 93%

“…In liver cells, for example, catecholamines, prostaglandin E1, and glucagon inhibit the Na+,K+ pump in a manner that is blocked by insulin, and these effects are related to changes in the intracellular concentration of cyclic AMP (11)(12)(13). In contrast, in frog skeletal muscle (14), rat soleus muscle (15), sympathetic ganglia (16), mouse brain synaptosomes (17), and atrial tissue (18)(19)(20), various catecholamines stimulate the activity of the jump. Finally, microinjection of Na+ into snail ganglia neurons has been shown to stimulate directly the Na+,K+ pump, leading to 20-mV hyperpolarization of the neuronal membrane (7,8).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mechanism of monensin-induced hyperpolarization of neuroblastoma-glioma hybrid NG108-15.

Lichtshtein¹,

Dunlop²,

Kaback³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Addition of the ionophore monensin to mouse neuroblastoma-rat glioma hybrid NG108-15 cells leads to a 20 to 30-mV increase in the electrical potential across the plasma membrane as shown by direct intracellular recording techniques and by distribution studies with the lipophilic cation 13H-tetraphenylphosphoniumt (TPP+) [Lichtshtein, D., Kaback, H. R. & Blume, A. J. (1979) Proc. NatL Acad. Sci. USA 76, 650-6541.The effect is not observed with cells suspended in high K medium, is dependent upon the presence of Na+ externally, and the concentration of monensin that induces half-maximal stimulation of TPP+ accumulation is approximately 1 pM. The ionophore also causes rapid influx of Na+, a transient increase in intracellular pH, and a decrease in extracellular pH, all of which are consistent with the known ability of monensin to catalyze the transmembrane exchange of H+ for Na+. Although ouabain has no immediate effect on the membrane potential, the cardiac glycoside completely blocks the increase in TPP+ accumulation observed in the presence of monensin. Thus, the hyperpolarizing effect of monensin is mediated apparently by an increase in intracellular Na+ that acts to stimulate the electrogenic activity of the Na+,K+-ATPase. Because monensin stimulates TPP± accumulation in a number of other cultured cell lines in addition to NG10815, the techniques described may be of general use for studying the Na+,K+ pump and its regulation' in situ.The Na+,K+-activated ATPase (Na+,K+'pump) (ATP phosphohydrolase, EC 3.6.1.3) is present in the membranes of excitable (1) and nonexcitable (2-4) tissues and represents a major pathway for Na+ and K+ transport across the plasma membrane of eukaryotic cells. Moreover, hydrolysis of ATP by this membranous enzyme is often accompanied by the simultaneous movement of three equivalents of Na+ out and two equivalents of K+ into the cell. This inequality in ion movements confers an electrogenic activity to the enzyme. That is, its activity results in the net outward movement of a positive current, which may lead to the generation of a membrane potential (AI, interior negative).Although the resting Az in nerve is due primarily to a K+ diffusion gradient ([K+Iin > [K+Iout), electrogenic Na+,K+-ATPase activity makes a contribution to A+I in certain cells (5, 6). Moreover, enhanced activity of the pump may have important consequences, because hyperpolarization will result. Presynaptically, this will lead to reduced transmitter release and postsynaptically, to decreased sensitivity to excitatory synaptic stimulation.Evidence has been presented indicating that the activity (7, 8) and coupling ratio-i.e., Na+ efflux/K+ influx (9, 10)-of the Na+,K+-ATPase are not constant, but are subject to regulation. In liver cells, for example, catecholamines, prostaglandin E1, and glucagon inhibit the Na+,K+ pump in a manner that is blocked by insulin, and these effects are related to changes in the intracellular concentration of cyclic AMP (11-13). In contrast, in frog skeletal muscle (14), rat s...

show abstract

“…In most of the investigations performed in working myocardium so far the cells were loaded with Na by various procedures and the resulting transient change in membrane potential (or clamp current) was measured (Page & Storm, 1965;Noma & Irisawa, 1975;Glitsch, Grabowski & Thielen, 1978). The interpretation of such experiments is complicated by the fact that the steady-state pump current and the change in intracellular Na must be inferred indirectly from the measured transients.…”

Section: Introductionmentioning

confidence: 99%

The electrogenic sodium pump in guinea‐pig ventricular muscle: inhibition of pump current by cardiac glycosides

Daut¹,

Rüdel

1982

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. The inhibition of the electrogenic sodium pump in guinea-pig ventricular muscle by cardiac glycosides was studied with a voltage-clamp technique.2. Superfusion of the preparation with dihydro-ouabain (DHO) produced a reversible depolarization of up to 7 mV. When the membrane potential was clamped to a constant value near the resting potential application of DHO produced a corresponding current change in the inward direction which reached a steady state in less than 1 min.3. The drug-induced current change (ID) was found to be the result of a parallel shift of the current-voltage relation. The contributions of a change in extracellular K or intracellular Na to the measured ID were shown to be very small. From these findings and the results summarized below it was concluded that ID represents the blockage of the electrogenic pump current by DHO and that it is proportional to the number of drug molecules bound to the Na-K-ATPase in the intact cell.4. The dependence ofID on the concentration of DHO applied (5 x 10-6-8 x 10-4 M) was found to be consistent with the predictions of the law of mass action for reversible one-to-one binding ofthe drug to the Na-K pump under equilibrium conditions. From a Scatchard-type plot the equilibrium dissociation constant (KD) of DHO was determined to be 4-6 (± 2'3) x 10-5 M.5. The steady-state pump current in the resting preparation was calculated to be 0-81 ±026 #sA/cm2. It contributed 6-4±09 mV to the resting potential in Tyrode solution containing 3 mm-K.6. In the smallest preparations used the measured time course of the onset and decay of ID agreed with the chemical kinetics of binding and unbinding calculated for various DHO concentrations. The rate constant of unbinding (k2) was found to be 3-4 (± 0 7) x 10-2 s-1 and the average rate constant of binding (k1) was 7-4 x 102 M-1 -1 7. By comparing the effects of ouabain and DHO in the same preparation the following estimates of the chemical constants of ouabain binding to the Na-K pump were obtained: KD = 15 X 10-6 M; k, = 4 x 103 M-1 s-1; k2 = 6 x 10-3 s-1. * Present address: Abteilung fur Allgemeine Physiologie, Universitit Ulm.

show abstract

Activation of the electrogenic sodium pump in guinea‐pig atria by external potassium ions

Cited by 50 publications

References 13 publications

Calcium Overload and Cardiac Function

Calcium Overload and Cardiac Function

Mechanism of monensin-induced hyperpolarization of neuroblastoma-glioma hybrid NG108-15.

The electrogenic sodium pump in guinea‐pig ventricular muscle: inhibition of pump current by cardiac glycosides

Contact Info

Product

Resources

About