The depressant effects of some amiloride analogues on the slow outward K+ current and contraction of voltage-clamped frog muscle fibres

Nasri-Sebdani, Mohammad; Cragoe, Edward J.; Cognard, Christian; Potreau, Daniel; Raymond, Guy

doi:10.1016/0014-2999(89)90433-0

Cited by 5 publications

(4 citation statements)

References 24 publications

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Section: Discussionmentioning

confidence: 99%

“…Since most ion channels would not be conductive in our solutions near Er with the exception of inward rectifier K+ channels, it is possible that this inconsistency can be explained by the partial blockage of these channels by amiloride. In fact, other K+ channels like delayed rectifier K+ channels of atrial myocytes (Bielefeld, Hadley, Vassilev & Hume, 1986) and slow K+ channels of frog muscle (Nasri-Sebdani, Cragoe, Cognard, Potreau & Raymond, 1989) (Renkin, 1961) and that very little changes in Er occur in frog muscle when Na+ is partially replaced by NMG (McKinney, 1984). Therefore, it is likely that K+ is also permeant through this channel and that Er approaches EK when Na+ is replaced by K+ (Fig.…”

Section: Effect Of Amiloride On Linear Membrane Constantsmentioning

confidence: 98%

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The effect of amiloride on the resting potential and the electrical constants of frog skeletal muscle fibres.

Estrada

Sánchez

1991

The Journal of Physiology

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SUMMARY1. The effects of amiloride on the membrane potential of frog skeletal muscle fibres were investigated with a single intracellular microelectrode. Two microelectrode current-and voltage-clamp experiments were also performed to determine the effects of amiloride on the electrical constants and membrane current near the resting potential.2. Amiloride reversibly hyperpolarized muscle fibres up to ca 12 mV in 2 5 mM-K+, in a concentration-dependent manner, with a half-maximum effect at 02 mm. Amiloride (0 4 mM) also significantly increased the membrane resistance of muscle fibres.3. The effects of amiloride were consistent with the classical theory of the resting potential and could be described by assuming that it removes the Na' permeability factor in the Goldman-Hodgkin-Katz equation for [K+]. > 2-5 mM.4. Replacement of [Na+]o by N-methyl-glucamine, choline or Mg2+ produced smaller effects on the resting potential and on membrane resistance than those induced by amiloride.5. It is concluded that an amiloride-sensitive poorly selective conductance continuously depolarizes the cellular membrane thus playing a role in the resting potential of frog skeletal muscle.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Amiloride On Linear Membrane Constantsmentioning

confidence: 98%

The effect of amiloride on the resting potential and the electrical constants of frog skeletal muscle fibres.

Estrada

Sánchez

1991

The Journal of Physiology

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“…), when the delayed rectifier IK is already partially activated. Amiloride derivatives albeit others than reported in this study were shown to depress slow outward current in frog skeletal cells (Nasri-Sebdani et al 1989).…”

Section: Discussionmentioning

confidence: 47%

“…All three drugs also impair Na+/ H + exchange (Vigne et al 1984) and various membrane conductances (e.g. Bielefeld et al 1986, Garcia et al 1990, Nasri-Sebdani et al 1989, Tang et al 1988, the impact of these effects on force of contraction are discussed below. Furthermore, force of contraction could be modulated by effects of the amiloride derivatives on various enzymatic activities.…”

Section: Discussionmentioning

confidence: 99%

Amiloride Derivatives as Blockers of Na⁺/Ca²⁺ Exchange: Effects on Mechanical and Electrical Function of Guinea‐Pig Myocardium

Wettwer

Himmel

Ravens

1992

Pharmacology & Toxicology

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The amiloride derivatives, 2',3'-benzobenzamil (BB), 3',4'-dichlorobenzamil (DCB), and 5-(N-4-chlorobenzyl)-2',4'-dimethylbenzamil (CBDB) are known as inhibitors of the Na+/Ca2+ exchange. This kind of drug action was recently suggested to be a new inotropic mechanism. In guinea-pig myocardium, we have studied the inotropic and the accompanying electrophysiological effects of the three compounds in order to assess their selectivity of action. In left atria and in papillary muscle, force of contraction increased with DCB and CBDB (atria only) at a high concentration (5 x 10(-5)-10(-4) mol/l) and after long exposure time, whereas BB produced a negative inotropic effect. In the isolated perfused Langendorff heart, the amiloride derivatives tested decreased spontaneous heart rate and force of contraction and prolonged the duration of contraction. In isolated cardiac myocytes, sodium current, calcium current and the delayed rectifier were reduced by concentrations of BB, DCB and CBDB similar to the IC50 values reported for the inhibition of the Na+/Ca2+ exchange. Our results demonstrate that the amiloride derivatives have multiple sites of action. It is concluded that more specific modulators of the Na+/Ca2+ exchange are required in order to define their contribution to the regulation of contractile activation of the heart.

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Role of Na-H exchangers and vacuolar H+ pumps in intracellular pH regulation in neonatal rat osteoclasts.

Ravesloot

Eisen

Baron

et al. 1995

The Journal of General Physiology

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Osteoclasts resorb bone by pumping of H + into a compartment between the cell and the bone surface. Intracellular pH (pHi) homeostasis requires that this acid extrusion, mediated by a vacuolar-type H + ATPase, be complemented by other acid-base transporters. We investigated acid-extrusion mechanisms of single, freshly isolated, neonatal rat osteoclasts. Cells adherent to glass coverslips were studied in the nominal absence of CO2/HCO~, using the pH-sensitive dye BCECF and a digital imaging system. Initial pHi averaged 7.31 and was uniform throughout individual cells. Intrinsic buffering power (l~l) decreased curvilinearly from ~ 25 mM at pHi = 6.4 to ~ 6.0 mM at pHi = 7.4. In all polygonally shaped osteoclasts, and ~ 60% of round osteoclasts (~ 20% of total), pHi recovery from acid loads was mediated exclusively by Na-H exchange. In these pattern-1 cells, pHi recovery was 95% complete within 200 s, and was blocked by removing Na +, or by applying 1 mM amiloride, 50 IxM ethylisopropylamiloride (EIPA), or 50 ~M hexamethyleneamiloride (HMA). The apparent K~/2 for HMA ([Na+]o = 150 mM) was 49 nM, and the apparent Kl/2 for Na § was 45 mM. Na-H exchange, corrected for amiloride-insensitive fluxes, was half maximal at pHi 6.73, with an apparent Hill coefficient for intracellular H § of 2.9. Maximal Na-H exchange averaged 741 IxM/s. In the remaining ~40% of round osteoclasts (pattern-2 cells), pHi recovery from acid loads was brisk even in the absence of Na § or presence of amiloride. This Na+-independent pHi recovery was blocked by 7-chloro-4-nitrobenz-2-oxa-l,3-diazol (NBD-C1), a vacuolar-type H § pump inhibitor. Corrected for NBD-C1 insensitive fluxes, H § pump fluxes decreased approximately linearly from 96 at pHi 6.8 to 11 txM/s at pHi 7.45. In ~45% of pattern-2 cells, Na + readdition elicited a further pHi recovery, suggesting that H § pumps and Na-H exchangers can exist

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The depressant effects of some amiloride analogues on the slow outward K+ current and contraction of voltage-clamped frog muscle fibres

Cited by 5 publications

References 24 publications

The effect of amiloride on the resting potential and the electrical constants of frog skeletal muscle fibres.

The effect of amiloride on the resting potential and the electrical constants of frog skeletal muscle fibres.

Amiloride Derivatives as Blockers of Na⁺/Ca²⁺ Exchange: Effects on Mechanical and Electrical Function of Guinea‐Pig Myocardium

Role of Na-H exchangers and vacuolar H+ pumps in intracellular pH regulation in neonatal rat osteoclasts.

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The depressant effects of some amiloride analogues on the slow outward K+ current and contraction of voltage-clamped frog muscle fibres

Cited by 5 publications

References 24 publications

The effect of amiloride on the resting potential and the electrical constants of frog skeletal muscle fibres.

The effect of amiloride on the resting potential and the electrical constants of frog skeletal muscle fibres.

Amiloride Derivatives as Blockers of Na+/Ca2+ Exchange: Effects on Mechanical and Electrical Function of Guinea‐Pig Myocardium

Role of Na-H exchangers and vacuolar H+ pumps in intracellular pH regulation in neonatal rat osteoclasts.

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Amiloride Derivatives as Blockers of Na⁺/Ca²⁺ Exchange: Effects on Mechanical and Electrical Function of Guinea‐Pig Myocardium