Comparison of the Effects of BDM on L-Type Ca Channels of Cardiac and Skeletal Muscle

Abstract

Effects of the compound 2,3 Butanedione monoxime (BDM) on force development have been described in skeletal muscle (Fryer et al., 1988), cardiac muscle (Bergey et al., 1981; West & Stephenson 1989) as well as in smooth muscle (Österman et al., 1993; Watanabe, 1993). It inhibits contraction acting at different levels: on the contractile mechanism as was shown by Horiuti et al. (1988) and Österman et al. (1993) and on the excitation-contraction coupling process (Hui & Maylie, 1991; De Armas et al., 1993; Li et al., 1985). In addition to these effects on contractility the drug reduces Ca“ current through L-type Ca²⁺ channels in cardiac (Coulombe et al., 1990; Chapman, 1992; Ferreira et al., 1993), skeletal muscle (Fryer et al., 1988) and smooth muscle (Lang & Paul, 1991). This reduction obeys to an enhanced voltage dependent inactivation of the channel (Chapman 1992, 1993; Ferreira et al., 1993). Since BDM is a chemical phosphatase, member of a group of oximes with the ability to reactivate cholinesterase after exposure to organo-phosphorous compounds (Wilson & Grinsberg, 1955), it has been suggested that dephosphorylation is the mechanism of action of the drug. Several experimental evidences recently provided are in line with this hypothesis (Chapman, 1993a; Chapman, 1995).