Effect of 2,3-butanedione 2-monoxime on slow inward and transient outward currents in rat ventricular myocytes.
The effect of 2,3-butanedione 2-monoxime (BDM), a substance possessing phosphatase-like activity, was studied on action potentials of isolated rat heart and on the slow inward calcium current and outward current (including the 4-aminopyridine (4-AP)-sensitive transient outward component), in rat ventricular myocytes. In contrast to what was observed by other authors in different species and cardiac tissues, BDM increased markedly the amplitude and duration of the rat ventricular action potential plateau. On the other hand, in the presence of 4-AP and ryanodine BDM shortened action potential duration. BDM decreased in a dose dependent manner the amplitude of both the slow inward calcium current and the transient outward current, accelerated their inactivation and shifted their steady-state inactivation-voltage relationships towards negative potentials. BDM also depressed other components of outward current. It is suggested that the lengthening effect of BDM on action potential duration results mainly from the simultaneous reduction of both the slow inward calcium current and the transient outward current, two antagonistic currents with unequal influences on action potential plateau development. The similarity of effect of BDM on these two currents also suggests that ionic channels generating them might require similar phosphorylation for their functioning.
Coulombe
A
A
Laboratoire de Physiologie Comparée associé au CNRS (URA 1121), Université Paris-Sud, Orsay, France.
Lefevre
I A
IA
Deroubaix
E
E
Thuringer
D
D
Coraboeuf
E
E
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles; D015640:Ion Channel Gating / Q000187:drug effects*; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology
D012433:Ryanodine; C004717:diacetylmonoxime; D015761:4-Aminopyridine; D003931:Diacetyl; D002118:Calcium