Effects of amiloride on calcium uptake by myocytes isolated from adult rat hearts

Altschuld, Ruth A.; Hohl, Charlene M.; Lamka, Karla G.; Brierley, Gerald P.

doi:10.1016/0024-3205(84)90412-0

Cited by 22 publications

(5 citation statements)

References 11 publications

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“…Amiloride at 1 mm has also been reported to block Na+-Ca2+ exchange in a wide variety of preparations including cardiac sarcolemmal vesicles (Siegl, Cragoe, Trumble & Kaczorowski, 1984;Floreani & Luciani, 1984) and isolated cardiac myocytes (Altschuld, Hohl, Lamka & Brierly, 1984). Since 01 mMamiloride almost totally inhibits Na+-H+ exchange in cultured chick heart cells (Piwnica-Worms et al 1985), testing the effects of amiloride at 0 1 and 1 mm should allow us to differentiate its effects on the two exchangers.…”

Section: Electrogenticity Of Na+-ca2+ Exchangementioning

confidence: 99%

Electrogenic sodium‐calcium exchange in cultured embryonic chick heart cells.

Jacob

Lieberman

Liu

1987

The Journal of Physiology

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SUMMARY1. The membrane potential (Em) of cultured chick embryonic heart cells depolarized to -36 mV after inhibition of the Na+-K+ pump by 0-1 mM-ouabain in a [K+]. of24 mM: this was accompanied by a rise in Na+ content of -65 % in 3 min. Lowering [Na+]. to 27 mm then caused a fall in Na+ content, a rise in Ca2+ content and a small hyperpolarization of -5 mV. The fall in Na+ content indicated a movement of Na+ which was in the opposite direction to the Na+ electrochemical gradient (a countergradient movement).2. In the presence of 10 mM-Cs+ or 1 mM-Ba2+ the hyperpolarization was -10 or 30 mV, respectively. A 30 mV hyperpolarization took Em negative to the reversal potentials for K+, Na+ and Cl-as measured by ion-selective micro-electrodes.3. The decay of the intracellular Na+ activity, aka, in an [Na+]o of 27 mM followed a simple exponential time course (time constant, 36 s). The initial rate depended on the value to which [Na+]. was lowered in a manner suggesting a simple competitive inhibition of the exchange by external Na+.4. The low- [Na+]. hyperpolarization was unaffected by amiloride (0-1 or 1 mM) or verapamil (20 /SM). Both La3+ (1 mM) and Mn2+ (20 mM) blocked the hyperpolarization sufficiently to prevent Em hyperpolarizing negative to the reversal potentials for K+, Na+ and Cl-. 6. We conclude that cultured embryonic chick heart cells contain a Na+{:Ca2+ exchange evidenced by the ability to cause movements of Na+ and Ca2+ which are counter to their respective electrochemical gradient and which are accompanied by downhill movements of the counter ion. In the presence of Ba2+ (which presumably blocks K+ permeability) the exchange is accompanied by a hyperpolarization which

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Section: Electrogenticity Of Na+-ca2+ Exchangementioning

confidence: 99%

Electrogenic sodium‐calcium exchange in cultured embryonic chick heart cells.

Jacob

Lieberman

Liu

1987

The Journal of Physiology

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“…The for amiloride for inhibiting Na influx in chick cardiac cells is 10 uM (Frelin et al 1984) and for inhibiting Na+ -Ca2+exchange in bovine sarcolemmal vessicles is 0.4 mM (Floreani et al 1984). Catecholamine-induced reduction in m a + ]i is produced by a different mechanism from amiloride which decreases m a + li in cardiac cells mainly by inhibition of Na+ -H+ exchange (Frelin et al 1984;Altschuld et al 1984). Thus two agents with different mechanisms of action that produce the same effect, namely a reduction in m a + ]i would be anticipated to potentiate each other as was observed herein.…”

Section: Isodroterenolmentioning

confidence: 70%

“…This decrease in ma+] i is the net effect of catecholamines on sodium transport that include catecholamine-induced stimulation of Na+-K+ pump activity, increase in passive Na+ influx and stimulation of active Na+ efflux (Gadsby 1983;Akasu et al 1978;Desilets & Baumgarten 1986). However it is not clear whether the functional effects of catecholamines on the heart are causally related to Na influx and alterations of p a + ] i. Elucidation of the role of Na+ influx under various conditions has been aided by the use of amiloride, a potent inhibitor of Na+ entry mainly due to its high affinity inhibition on Na+-Hf exchange (Benos 1982) that may involve a pathway that accounts for as much as 50% of basal Na+ permeability in cardiac cells (Frelin et al 1984;Altschuld et al 1984;Piwnica-Worms & Lieberman 1983). An interaction between amiloride and catecholamines has been suggested as amiloride ameliorates catecholamine-induced cardiac arrhythmias and myocardial necrosis in the intact animal (Selye 1969;Rabkin & Roob 1987).…”

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confidence: 99%

The Effect of Amiloride on the Cardiac Chronotropic Responses to Isoproterenol in Myocardial Aggregate Cells in Culture

Rabkin

1990

Pharmacology & Toxicology

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The purpose of this study was to test the hypothesis that amiloride alters the response of cardiac myocytes to isoproterenol. Myocardial cell aggregates were prepared from 7 day-old chick embryos maintained in culture for 72 hrs before study. Isoproterenol, 10-8 M to 10-5 M, significantly (P less than 0.05) increased contractile frequency of myocardial aggregates. The effects of isoproterenol were maximum within 5 min. of exposure and declined thereafter. In the absence of isoproterenol, amiloride, at 10-6 M and 10-7 M produced a transient decrease in contractile frequency while amiloride at 10-5 M produced a significant (P less than 0.05) decrease in contractile frequency. Amiloride significantly (P less than 0.05) increased the effect of isoproterenol on cardiac contractile frequency. There was a greater and more sustained response to isoproterenol in the presence of amiloride. Furthermore, the magnitude of these effects were greater with higher concentrations of amiloride. These data indicate that amiloride accentuates the cardiac chronotropic response to isoproterenol and suggest that, because amiloride inhibits sodium entry in these cells, change in intracellular sodium may be one of the mechanisms mediating the chronotropic action of isoproterenol on the heart.

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“…It undoubtedly involves inhibition of Na* entry into the myocyte as amiloride is a potent inhibitor of sodium entry in a wide variety o f tissues including the heart [3], Amiloride's inhibition o f Na+ transport across cells has been divided into high and low affinity inhibitory properties. The high affinity inhibition is on the Na+-H+ exchange [4][5][6]. Because this process in cardiac cells may involve a pathway that accounts for as much as 50% o f basal Na+ permeability [4][5][6], it has been proposed to be the site o f interaction o f digitalis and amiloride [4], Amiloride has low-affinity inhibitory prop erties on Na+-Ca2+ exchange across the sarcolemma o f cardiac myocytes [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…The high affinity inhibition is on the Na+-H+ exchange [4][5][6]. Because this process in cardiac cells may involve a pathway that accounts for as much as 50% o f basal Na+ permeability [4][5][6], it has been proposed to be the site o f interaction o f digitalis and amiloride [4], Amiloride has low-affinity inhibitory prop erties on Na+-Ca2+ exchange across the sarcolemma o f cardiac myocytes [4][5][6]. Because digitalis increases intracellular calcium con centration through Na+-Ca2+ exchange, as a response to the increased [Na+]j produced by digitalis [7,8], other investigators have pro posed that amiloride may affect the cardiac response to digitalis by inhibition o f Na7-Ca2+ exchange [2], Hydrophobic substitution at the terminal nitrogen atom o f the guani dinium moiety of amiloride improves the inhibitory potency for Na+/Ca2+ exchange [9, 10], 3,,4'-Dichlorobenzamil is one o f the most potent o f these inhibitors [9,10].…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Effect of Amiloride and Its Analogue Dichlorobenzamil on Cardiac Chronotropic Responses to Ouabain in Myocardial Cell Aggregates in Culture

Rabkin¹

1989

Pharmacology

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The purpose of this study was to compare the effects of amiloride, an inhibitor of Na⁺-H⁺ exchange, and its analog 3’,4’-dichlorobenzamil, a more specific inhibitor of Na⁺-Ca²⁺ exchange on the response of cardiac myocytes to ouabain. Cardiac myocyte aggregates were prepared from myocytes obtained from 7-day-old chick embryo hearts. Ouabain at 10^–6M produced a marked and significant (p < 0.05) reduction in contractile frequency. Amiloride, at 10^–7 to 10”5 M produced a definite, significant (p < 0.05) and dose-dependent reduction in this effect of ouabain. In contrast, dichlorobenzamil, 10^–7 to 10^–6M, significantly (p < 0.05) accentuated this effect of ouabain. Thus, amiloride and its analog dichlorobenzamil have different effects on the cardiac responses to ouabain presumably because of the differences in the specificity of their inhibition of Na⁺/H⁺ and Na⁺/Ca²⁺ exchange. Thus to the extent that the effects of amiloride and dichlorobenzamil are mediated through, respectively Na⁺-H⁺ and Na⁺-Ca²⁺ exchange, these data suggest that ouabain-induced reduction in contractile frequency is mediated through Na⁺-H⁺ exchange while Na⁺-Ca²⁺ exchange acts to minimize this action of ouabain. Amiloride may be useful to oppose the negative chronotropic effect of ouabain while dichlorobenzamil accentuates this effect of ouabain.

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Effects of amiloride on calcium uptake by myocytes isolated from adult rat hearts

Cited by 22 publications

References 11 publications

Electrogenic sodium‐calcium exchange in cultured embryonic chick heart cells.

Electrogenic sodium‐calcium exchange in cultured embryonic chick heart cells.

The Effect of Amiloride on the Cardiac Chronotropic Responses to Isoproterenol in Myocardial Aggregate Cells in Culture

Comparison of the Effect of Amiloride and Its Analogue Dichlorobenzamil on Cardiac Chronotropic Responses to Ouabain in Myocardial Cell Aggregates in Culture

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