EFFECTS OF 8-(N-N-DIETHYLAMINO)OCTYL-3,4,5-TRIMETHOXYBENZOATE HYDROCHLORIDE (TMB-8) ON SKINNED MYOCARDIAL FIBERS OF THE RAT - REVERSIBLE INHIBITION OF CALCIUM-RELEASE FROM THE SARCOPLASMIC-RETICULUM

The effects of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydr ochloride (TMB-8), which is reported to inhibit the release of intrace llularly stored Ca2+ in skeletal and smooth muscles, were examined in ventricular myocardia of the adult rat. In skinned papillary muscle fi bres with functional sarcoplasmic reticulum (SR) preserved, applicatio n of 100 or 300 mu M TMB-8 during the Ca2+ loading period had no signi ficant effect on the peak tension of subsequent caffeine-induced contr action, but when applied during exposure to caffeine, concentration-de pendent reduction of the peak tension was observed. At 1000 mu M, TMB- 8 reduced the peak tension of caffeine-induced contraction when applie d either during Ca2+ loading or during exposure to caffeine. TMB-8 had no substantial influence on the Ca2+-tension of skinned fibres withou t functional SR. In isolated papillary muscle preparations, TMB-8 prol onged the action potential duration and decreased the maximum rate of rise of potential, leading to abolition of contraction at 100 mu M. In conclusion, TMB-8 may be a useful pharmacological tool for inhibiting Ca2+ release from SR, but only in skinned myocardial preparations.