Butanedione monoxime promotes voltage-dependent inactivation of L-type calcium channels in heart. Effects on gating currents

The effect of 20 mM extracellularly applied 2,3-Butanedione monoxime (BDM) on L-type Ca2+ channel charge movement current was studied in whole-cell voltage-clamped guinea-pig ventricular myocytes. Intramembraneous charge movement in response to depolarizing pulses (charge 1), was reduced after the a...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 1997-02, Vol.29 (2), p.777-787
Main Authors: Ferreira, G, Artigas, P, Pizarro, G, Brum, G
Format: Article
Language:English
Subjects:
Animals
Barium - metabolism
Barium - pharmacology
Calcium - metabolism
Calcium - pharmacology
Calcium Channels - drug effects
Calcium Channels - metabolism
Cells, Cultured
Diacetyl - analogs & derivatives
Diacetyl - pharmacology
Electric Conductivity
Guinea Pigs
Heart - drug effects
Ion Channel Gating - drug effects
Myocardium - cytology
Myocardium - metabolism
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Summary:The effect of 20 mM extracellularly applied 2,3-Butanedione monoxime (BDM) on L-type Ca2+ channel charge movement current was studied in whole-cell voltage-clamped guinea-pig ventricular myocytes. Intramembraneous charge movement in response to depolarizing pulses (charge 1), was reduced after the application of BDM. The effect was more pronounced at the OFF of the charge transient (41%) than at the ON (7%). The steady-state availability curve of charge 1 was shifted to the left; the magnitude of the voltage shift was similar to the shift in Ca2+ current availability. Charge movement recorded in the negative voltage range (charge 2) after conditioning depolarizing pulses of different duration, was increased by BDM. For a 300-ms conditioning pulse charge 2 measured during a negative test pulse increased 40% (in Ba2+ external solution) or 35% (in Ca2+ external solution). These results show that BDM promotes voltage-dependent inactivation of L-type Ca2+ channels in parallel with charge interconversion between intramembranous charges 1 and 2. Mechanistically they are consistent either with dephosphorylation or a dihydropyridine-like action, but argue against open channel block as the mechanism of the effect of the drug.
ISSN:0022-2828
DOI:10.1006/jmcc.1996.0321