Low concentrations of UD-CG 212 enhance myocyte contractility by an increase in calcium responsiveness in the presence of inorganic phosphate.

Recent data show that UD-CG 212 in nanomolar concentrations increases myofibrillar Ca++ responsiveness of chemically skinned cardiac preparations in the presence of elevated inorganic phosphate. We studied the effects of UD-CG 212 on cell shortening of intact myocytes and in addition measured the intracellular calcium transients with the aid of INDO-1 fluorescence in the presence of 5 mM inorganic phosphate. The validity of our experimental system was first tested with the calcium channel opener Bay k 8644. Bay k 8644 at 10(-8) M did not significantly influence myocyte shortening (+ 13.9 +/- 4.6%, n = 9) but at 10(-7) M and 10(-6) M significantly increased contraction by 40.1 +/- 13.6% and 52.5 +/- 17.0% respectively. Bay k 8644 at 10(-8) M increased the INDO-1 fluorescence ratio by 17.3 +/- 4.7% (P < 0.01; n = 9), and at 10(-7) M by 21.5 +/- 4.3% (P < 0.01; n = 9), whereas 10(-6) M Bay k 8644 had no significant effect on peak INDO-1 ratio. However, 10(-7) and 10(-6) M Bay k 8644 accelerated and broadened the calcium transients.(ABSTRACT TRUNCATED AT 250 WORDS)