INFLUENCE OF STIMULATION FREQUENCY ON [NA-PERFUSED RAT-HEART(](I) ANDCONTRACTILE FUNCTION IN LANGENDORFF)

To study the relationship between stimulation frequency and intracellu lar Na+ concentration ([Na+](i)), Langendorff-perfused rat hearts were loaded with the Na+-sensitive dye sodium-binding benzofuran isophthal ate SBFI). An intracellular calibration procedure allowed SBFI fluores cence to be transformed into [Na+](i). Compartmentation of SBFI was ev aluated by permeabilizing sarcolemmal membranes with saponin and subce llular compartments with Triton X-100. Most of the indicator was locat ed in the myoplasm (69%). When stimulation frequency was increased fro m 0 to 6 Hz, [Na+](i) increased from 3.0 to 7.9 mM, whereas pressure a mplitude (PA) declined to 49% of the maximum recorded at 2 Hz. Blockin g sarcoplasmic reticulum (SR) Ca2+ uptake with 2,5-di(tert-butyl)-1 ,4 -benzohydroquinone (TBQ; 10 mu M) at 2 Hz increased [Na+](i) from 4.9 to 8.4 mM and decreased PA by 70%. Raising stimulation frequency then resulted in a further increase in [Na+](i) and decline in PA. In concl usion, these data indicate that the rat heart is characterized by a ne gative pressure-frequency relationship associated with increasing [Na](i) at higher heart rates. After inhibition of SR Ca2+ uptake, [Na+]( i) further increases, whereas PA declines with increasing stimulus fre quency. It is suggested that part of the rise of [Na+](i) with stimulu s frequency and TBQ may be associated with increased Ca2+ extrusion an d Na+ influx on the Na+/Ca2+ exchange system.