EFFECTS OF POLYAMINES ON VOLTAGE-ACTIVATED CALCIUM CHANNELS IN GUINEA-PIG INTESTINAL SMOOTH-MUSCLE

Effects of polyamines on the spontaneous mechanical and electrical act ivity of guinea-pig intestinal smooth muscle were studied. Spermine an d spermidine inhibited action potential generation and contractions, w hile putrescine had no effect. Single smooth muscle cells were isolate d from the longitudinal muscle layer of the guinea-pig ileum. Whole-ce ll voltage-clamp experiments were carried out to investigate the effec ts of polyamines on current through voltage-activated Ca2+ channels. S permine and spermidine (0.1-1 mM) reduced the inward current in a conc entration-dependent manner. Spermine blocked current activated by the dihydropyridine agonist BAY K 8644 (1 mu M), whereas no additional inh ibition by spermine was seen after blockage of dihydropyridine-sensiti ve channels by nifedipine (0.1 mu M). Inhibition by spermine or spermi dine did not shift the peak of the current voltage relation of the inw ard current. Steady-state activation and inactivation relationships we re not affected and thus the amplitude, but not the voltage dependence , of the window current responsible for Ca2+ inflow during sustained d epolarization was affected. Putrescine (1 mM) had no significant effec t on the inward current. These results suggest that spermine and sperm idine inhibit contraction in spontaneously active intestinal smooth mu scle by inhibiting Ca2+ current responsible for generation of action p otentials.