DIFFERENTIAL ACTIONS OF EXOGENOUS AND INTRACELLULAR SPERMINE ON CONTRACTILE ACTIVITY IN SMOOTH-MUSCLE OF RAT PORTAL-VEIN

Effects of the naturally occurring polyamine spermine on electrical an d contractile properties of the rat portal vein were studied. 1 mM spe rmine nearly abolished spike activity and spontaneous contractions and decreased the intracellular Ca2+ concentration ([Ca2+](i)). The phasi c force responses to 0.1 and 1 mu M phenylephrine were partially inhib ited, but not the sustain plateau contraction caused by 5 mu M phenyle phrine. The Ca2+-force relation in high-K+ (128 mM)-depolarized veins was shifted to the right, EC(50) for Ca2+ increasing from 0.50 +/- 0.0 3 mM (control, n = 8) to 0.65 +/- 0.06 and to 0.94 +/- 0.03 at 1 (n = 4) and 10 (n = 3) mM spermine, respectively. However, at a Ca2+ concen tration of 2.5 mM, giving maximal force, there was no effect of spermi ne (1 mM) on either force or [Ca2+](i). Whereas extracellular spermine thus reduced contractile activity at moderate levels of stimulation, increased intracellular concentration of spermine potentiated the forc e response to Ca2+. Intracellular loading of spermine by reversible pe rmeabilization increased its concentration by 2-3 times. The spontaneo us activity and response to phenylephrine were unchanged. However, the Ca2+-force relation of depolarized veins was shifted to the left, EC( 50) decreasing from 0.51 +/- 0.04 mM in controls (n = 7) to 0.36 +/- 0 .02 mM in the loaded veins (n = 9). Spermine increased Ca2+-activated force in portal veins permeabilized with beta-escin. The degree of pot entiation was consistent with observed effects in spermine-loaded inta ct veins. The results suggest that spermine at physiological intracell ular concentration may contribute to the determination of Ca2+ sensiti vity in vascular smooth muscle cells.