2,3-Butanedione monoxime (BDM) decreases sarcoplasmic reticulum Ca content by stimulating Ca release in isolated rat ventricular myocytes

Abstract

The effects of 2,3-butanedione monoxime (BDM) were examined using rat ventricular myocytes loaded with Indo-1 to measure the intracellular Ca concentration ([Ca2+]i). BDM (10 mM) produced a transient increase of the systolic Ca transient with no steady-state effect on its magnitude. This transient increase was more marked when BDM was applied after having decreased the external Ca concentration from 1 to 0.1 mM. There was a transient increase of resting [Ca2+]i in both quiescent and electrically stimulated cells. Prior application of BDM decreased the rise of [Ca2+]i produced by caffeine. In voltage-clamped cells the rise of [Ca2+]i produced by BDM was accompanied by a transient inward current attributed to the electrogenic Na-Ca exchange. The amount of Ca lost from the cell upon application of 10 mM BDM could be estimated either from the integral of the BDM-evoked current or from the reduction of the integral of a caffeine-evoked current and corresponded to about 50% of the sarcoplasmic reticulum (s.r.) Ca content. The decrease of s.r. Ca content and the transient potentiation of the systolic Ca transient suggest that BDM acts by stimulating Ca-induced Ca release. These effects must be allowed for when using BDM.

F‐actin‐based Ca signaling—a critical comparison with the current concept of Ca signaling

“…The lower dynamic stability of the undecorated filament results in transient liberation of Ca-ADP-G-actin subunits from the barbed ends accompanied by Ca dissociation. This type of Ca release may have been observed recently by Turvey et al (2003), by Steele and Smith (1993) and Adams et al (1998) using the myosin ATPase inhibitor 2,3-butanedione monoxime (BDM). BDM is an effective inhibitor of the myosin actin interaction.…”

2,3-Butanedione Monoxime Suppresses Primarily Total Calcium Handling in Canine Heart.

“…Working points away from this encircled area on the BDM N-R line as well as the control N-R line requires futile Ca 2ϩ cycling (NϾ0) and R values greater than 0.15. However, no data exists in literature [1][2][3][4][5][6][7][8][9][10][11][12] to suggest that BDM increases R (i.e., the reactivity of E max to total Ca 2ϩ handling). Therefore, a reasonable working point under BDM cannot exist on the BDM (dashed) N-R lines except where the R-axis intercepts within the same shaded rectangle in Fig.…”

“…Some studies indicate that BDM suppresses primarily crossbridge force development without suppressing intracellular Ca 2ϩ transient in the myocardium [6][7][8]. Other reports indicate that BDM suppresses simultaneously or even primarily the Ca 2ϩ influx as well as the Ca 2ϩ store in the sarcoplasmic reticulum (SR) and its release in the myocardium [9][10][11][12]. However, their relative contributions to depressed contractility are still controversial in the mammalian (including human) myocardium [1][2][3][4][5][6][7][8][9][10][11][12].…”

Left Ventricular Mechanoenergetics in Small Animals

“…Consequently, in mouse slices, as in rat myocardial slices, the possibilities that delta mVO 2 for the residual cross-bridge cycling is negligibly small and that the BDM-induced definite decrease in delta mVO 2 is due to the inhibition of Ca 2+ handling in E-C coupling are highly supportable. In fact, many reports show that BDM decreases energy expenditure utilized for total Ca 2+ handling in E-C coupling [153][154][155][156]. The motility index indicates only residual crossbridge cycling at a mechanically unloaded state, and thus motility is originally small.…”