Oximes: ‘Enzymatic’ slow channel antagonists in canine cardiac purkinje fibers?

Bergey, James L.; Reiser, Joseph; Wiggins, Jay R.; Freeman, Alan R.

doi:10.1016/0014-2999(81)90033-9

Cited by 24 publications

(11 citation statements)

References 22 publications

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“…The mechanism for the decrease in the sarcolemmal calcium current is controversial since some laboratories link the inhibition to the phosphatase activity of BDM (Bergey et al, 1981;Huang & McArdle, 1992) while other laboratories have found no correlation with its phosphatase activity and suggest a direct effect on the channel (Lang & Paul, 1991;Schlichter et al, 1992;Zhu & Ikeda, 1993). Another explanation might be inhibition of sarcolemmal calcium current by an elevation of intraceUular Ca 2+ resulting from a BDM-induced release of Ca 2+ from the SR.…”

Section: Contractile Apparatusmentioning

confidence: 99%

The effect of 2,3-butanedione 2-monoxime (BDM) on ventricular trabeculae from the avian heart

Brotto

Fogaça

Creazzo

et al. 1995

J Muscle Res Cell Motil

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2,3-butanedione 2-monoxime (BDM, 3-30 mM) decreased twitch force of intact ventricular trabeculae isolated from 19-day embryonic chick hearts in a dose-dependent manner. The responses to BDM were rapid and reversible. In an attempt to determine the cellular basis for the inhibitory effect of BDM, experiments were carried out on skinned muscle fibres and isolated myocytes. In trabeculae skinned with Triton X-100, BDM depressed maximum calcium activated force (Fmax) with an IC50 of 14 mM. At 3 mM BDM, the proportional decrease in twitch force in intact tissue was similar to that of Fmax in skinned tissue. At higher BDM concentrations (10 and 30 mM), however, the proportional decrease in twitch force was greater than that of Fmax. BDM (up to 10 mM) had no effect on the normalized force-pCa relationship. In saponin-skinned preparations, BDM (3 and 30 mM) released calcium from the fully loaded sarcoplasmic reticulum to a slightly greater extent in the absence of calcium (pCa 8.5) than in the presence of a fixed level of free calcium (pCa 5.5). Whole cell patch clamping of freshly isolated chick myocytes demonstrated that BDM caused a dose-dependent decrease in the T- and L-type calcium current. Therefore, at low BDM concentrations (3 mM), the decrease in twitch force can be ascribed predominantly to depression of the contractile apparatus while, at higher concentrations of BDM, there is an additional inhibitory effect of BDM on excitation-contraction coupling.

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Section: Contractile Apparatusmentioning

confidence: 99%

The effect of 2,3-butanedione 2-monoxime (BDM) on ventricular trabeculae from the avian heart

Brotto

Fogaça

Creazzo

et al. 1995

J Muscle Res Cell Motil

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“…This inhibition was attributed to dephosphorylation causing inactivation of the ion channels underlying this current. In subsequent studies, Bergey et al (1981) demonstrated that 2,3-butanedione monoxime suppressed slow action potentials of canine cardiac Purkinje fibres treated with isoprenaline or tetraethylammonium.…”

Section: Contractile Effectsmentioning

confidence: 99%

Multiple Effects of 2,3‐Butanedione Monoxime

Sellin¹,

McArdle²

1994

Pharmacology & Toxicology

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Ahstr0rc.r: 2,3-Butanedione monoxime. also known as diacetyl monoxime, is a nucleophilic agent which dephosphorylates iicetylcholinesterase poisoned with organophosphates. This "chemical phosphatase" activity stimulated studies of the effect of 2.3-butanedione monoxime on phosphorylation-dependent cellular processes. As a result of these studies, we know that the drug affects a number of mechanisms including muscle contraction, ionic current flow and synaptic transmission. Furthermore. it may he used as a component of cardioplegic solutions since it protects cardiac tissue exposed to certain ischaemic conditions. While this MiniRewiev reveals the diversity of its cellular actions. there continues LO be unresolved questions regarding its molecular mechanism.

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“…At higher concentrations, BDM (2-10 mM) decreased the sensitivity of the contractile apparatus to Ca21 (Li, Sperelakis, Teneick & Solaro, 1985;Fryer et al 1988b) and modified the number of interacting cross bridges (Blanchard et al 1988). The Ca2+ action potential in cardiac muscle and the Ca2+ current in skeletal muscle were also reduced by these high concentrations of BDM (Bergey, Reiser, Wiggins & Freeman, 1981; Wiggins, Reiser, Fitzpatrick & Bergey, 1980;Li et al 1985;Fryer et al 1988a). Little information is available on the action of BDM in smooth muscle.…”

Section: Introductionmentioning

confidence: 99%

“…ATPyS and the action of BDM BDM was originally thought to have phosphatase-like activity (Wilson & Ginsberg, 1955;Green & Saville, 1956) and such an action has been evoked recently to explain TAENIA CAECI CELLS AND Ca2`CHANNEL BLOCKERS some of its inhibitory action in skeletal and cardiac muscle (Wiggins et al 1980;Bergey et al 1981;Fryer et al 1988b). It may be that BDM is dephosphorylating Ca2+ channels in smooth muscle which modifies their kinetics and/or number to produce the smaller, more rapidly inactivating Ca2+ channel currents recorded.…”

Section: Bay K 8644 Antagonizes Bdmmentioning

confidence: 99%

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Effects of 2,3‐butanedione monoxime on whole‐cell Ca2+ channel currents in single cells of the guinea‐pig taenia caeci.

Lang

Rutgeerts

1991

The Journal of Physiology

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SUMMARY1. The inhibitory actions of cadmium (Cd2+), nifedipine and 2,3-butanedione monoxime (BDM) on whole-cell Ca21 channel currents in single cells of the guinea-pig taenia caeci were investigated using a single-electrode whole-cell voltage-clamp technique.2. Calcium channel currents were isolated using pipette solutions containing Cs+, tetraethylammonium and ATP (3 mM). Ca2+ or Ba2+ (7-5 mM) in the bathing solution acted as the charge carrier during inward current flow. Ca2+ channel currents in 7.5 mM-Ba2+ (IBa) were recorded at potentials positive to -40 mV, were maximal near 0 mV and reversed near + 60 mV. Ca2+ channel activation showed a sigmoidal relationship with potential, which was half-maximal at -13 mV.3. Both the inward and outward flow of current was depressed and eventually blocked by 0 3-100 ,tM-Cd2+, 0 1-10 ftM-nifedipine and 2-20 mm-BDM. Half-maximal blockade of IBa at 0 mV was achieved with -3 /tM-Cd2 , 1 /LM-nifedipine and 10 mM-BDM. Steady-state activation curves were not affected by Cd2+ or BDM, but were shifted in the hyperpolarizing direction by nifedipine at concentrations > 1 /,M.4. Calcium channel currents in single cells and K+ contractures in intact strips were both blocked in a voltage-dependent manner. Steady-state inactivation curves (f.o(V)) for IBa were shifted 20 mV in the hyperpolarizing direction by 0-3 /iMnifedipine and 4 mV by 10 mM-BDM. From these shifts a dissociation binding constant to inactivated Ca2+ channels for nifedipine was estimated as 78 nm, and for BDM, 5 mM.5. At 10/M Cd2+ produced a 43 + 6 % (n = 3) block of the inward current at 0 mV when Ca2+ (7 5

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Oximes: ‘Enzymatic’ slow channel antagonists in canine cardiac purkinje fibers?

Cited by 24 publications

References 22 publications

The effect of 2,3-butanedione 2-monoxime (BDM) on ventricular trabeculae from the avian heart

The effect of 2,3-butanedione 2-monoxime (BDM) on ventricular trabeculae from the avian heart

Multiple Effects of 2,3‐Butanedione Monoxime

Effects of 2,3‐butanedione monoxime on whole‐cell Ca2+ channel currents in single cells of the guinea‐pig taenia caeci.

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