2,3-Butanedione monoxime (BDM) decreases sarcoplasmic reticulum Ca content by stimulating Ca release in isolated rat ventricular myocytes.
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.
Adams
W
W
Department of Veterinary Preclinical Sciences, University of Liverpool, Liverpool L69 3BX, UK.
Trafford
A W
AW
Eisner
D A
DA
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002863:Chromogenic Compounds; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D007211:Indoles / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019188:Organ Preservation Solutions; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism
D002863:Chromogenic Compounds; D007211:Indoles; D019188:Organ Preservation Solutions; C004717:diacetylmonoxime; D002110:Caffeine; D003931:Diacetyl; C048960:indo-1; D002118:Calcium