Dual action of prajmalium on the Ca currents in frog isolated cardiomyocytes

Álvarez, Julio L.; Vassort, Guy

doi:10.1016/0022-2828(91)90054-p

Cited by 6 publications

(5 citation statements)

References 35 publications

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“…The reversal potential for/car is estimated to be near to +50 mV and that for/CaT between +20 and +30 mV. These values are very similar to those reported by others in frog atrial and ventricular cells (Argibay et al, 1988;Campbell et al, 1988b;Bonvallet and Rougier, 1989;Alvarez and Vassort, 1991). IcaL inactivates between -40 and 0 mV, with a potential for half-inactivation around -30 mV.…”

Section: Discussionsupporting

confidence: 87%

“…The most salient features of this work are the complex voltage dependence of/CaT kinetics and the sensitivity of /CaT tO several pharmacological agents as well as to neuromediators. Previous results obtained in cardiac cells isolated from the same (Bean, 1985a;Alvarez and Vassort, 1991) and another (Bonvallet, 1987;Bonvallet and Rougier, 1989) species of the same genus already suggested the existence of two Ca currents. On the other hand, Campbell et al (1988a, b) found no evidence of the existence of /CaT in the bullfrog atrial cells.…”

Section: Discussionmentioning

confidence: 81%

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Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current.

Álvarez

Vassort

1992

The Journal of General Physiology

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The properties of the low threshold Ca current (/CAT) in bullfrog (Rana catesbeiana) isolated atrial cardiomyocytes were studied using the whole-cell recording patch-damp technique and compared with those of the high threshold Ca current (IC~L). In 91% of atrial cells we observed both lc~-r and IC~L when collagenase and trypsin were used to dissociate the cells. But when pronase was used, only 30% of the cells exhibited loT. Icax was never found in ventricular cells. /CaT could be investigated more easily when ICaL was inhibited by Cd ions (50 p.M). Its kinetics were unchanged by substituting Ba for Ca, or in the presence of high concentrations of Ba. Both lcax and IC~L exhibited reduced inactivation after high depolarizing prepulses, lcax was found to be sensitive to dihydropyridines: 1 ~,M nifedipine decreased this current while 1 ~M BAY K 8644 increased it; this occurred without significant variations in the steady-state inactivation curve. /CaT was more sensitive than IcaL to cq-adrenergic and P2-purinergic stimulations, while ICaL was more sensitive to [3-adrenergic stimulation. Isoproterenol was still able to increase Icax in the presence of high intracellular cAMP. Both currents were increased by 1 ~M ouabain (although ICaL only transiently) and decreased by 10 I~M ouabain. It is concluded that the two types of Ca channels can be observed in bullfrog atrial cells and that they are specifically altered by pharmacological agents and neuromediators. This may have implications for cardiac behavior.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 81%

Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current.

Álvarez

Vassort

1992

The Journal of General Physiology

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“…For voltage‐gated Na + channels, plant alkaloids, including ajmaline, act at six or more distinct receptor sites on the channel protein ( Wink, 1993 , 2000 ; Cestele and Catterall, 2000 ). Further evidence comes from blocking effects of ajmaline on L‐type Ca 2+ currents in ventricular myocytes ( Bebarova et al ., 2005b ) and dual effects of prajmaline on Ca 2+ currents in frog cardiomyocytes ( Alvarez and Vassort, 1991 ). This is expected from the high homology of the voltage‐dependent Na + , K + and Ca 2+ channels ( Catterall, 1988 ; Lehmann‐Horn and Jurkat‐Rott, 1999 ).…”

Section: Discussionmentioning

confidence: 99%

NA⁺‐ and K⁺‐channels as molecular targets of the alkaloid ajmaline in skeletal muscle fibres

Friedrich

Wegner

Fink

2007

British J Pharmacology

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Background and purpose: Ajmaline is a widely used antiarrhythmic drug. Its action on voltage-gated ion channels in skeletal muscle is not well documented and we have here elucidated its effects on Na þ and K þ channels. Experimental approach: Sodium (I Na ) and potassium (I K ) currents in amphibian skeletal muscle fibres were recorded using 'loose-patch' and two-microelectrode voltage clamp techniques (2-MVC). Action potentials were generated using current clamp. Key results: Under 'loose patch' clamp conditions, the IC 50 for I Na was 23.2 mM with Hill-coefficient h ¼ 1.21. For I K , IC 50 was 9.2 mM, h ¼ 0.87. Clinically relevant ajmaline concentrations (1-3 mM) reduced peak I Na by B5% but outward I K values were reduced by B20%. Na þ channel steady-state activation and fast inactivation were concentration-dependently shifted towards hyperpolarized potentials (B10 mV at 25 mM). Inactivation curves were markedly flattened by ajmaline. Peak-I K under maintained depolarisation was reduced to B30% of control values by 100 mM ajmaline. I K activation time constants were increased at least two-fold. Lower concentrations (10 or 25 mM) reduced steady-state-I K slightly but peak-I K significantly. Action potential generation threshold was increased by 10 mM ajmaline and repolarisation prolonged. Conclusions and implications: Ajmaline acts differentially on Na þ and K þ channels in skeletal muscle. This suggests at least multiple sites of action including the S4 subunit. Our data may provide a first insight into specific mechanisms of ajmaline-ion channel interaction in tissues other than cardiac muscle and could suggest possible side-effects that need to be further evaluated.

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“…At a concentration of 1 nM, prajmalium increased I, , by 30% while at 1 pM prajmalium decreased it by 55% (3). The effects of prajmalium on EaT were accompanied by an increase in its rate of inactivation and a small shift to more hyperpolarized potentials of the availability curve.…”

Section: Ca2+ Currents (I and Icat)mentioning

confidence: 96%

“…In addition, the increase in ICaL was additive to maximal P-adrenergic and P,-purinergic stimulations Due to its lipophilic nature, multiple effects of prajmalium are to be expected. In this sense prajmalium shares similar actions on I, , with those of dihydropyridines: stimulation-inhibition depending on concentration, voltage-dependent effects, and speeding up of inactivation (3). Whether there are two receptor sites for prajmalium within the Ca" channels, with different affinities or one site with "voltage-dependent affinities" or even non-specific actions of the drug in the membrane nearby the Ca2+ channel, remains to be elucidated.…”

Section: Ca2+ Currents (I and Icat)mentioning

confidence: 98%

Prajmalium

Álvarez

Vassort

1993

Cardiovascular Drug Reviews

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Dual action of prajmalium on the Ca currents in frog isolated cardiomyocytes

Cited by 6 publications

References 35 publications

Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current.

Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current.

NA⁺‐ and K⁺‐channels as molecular targets of the alkaloid ajmaline in skeletal muscle fibres

Prajmalium

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Dual action of prajmalium on the Ca currents in frog isolated cardiomyocytes

Cited by 6 publications

References 35 publications

Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current.

Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current.

NA+‐ and K+‐channels as molecular targets of the alkaloid ajmaline in skeletal muscle fibres

Prajmalium

Contact Info

Product

Resources

About

NA⁺‐ and K⁺‐channels as molecular targets of the alkaloid ajmaline in skeletal muscle fibres