Inward rectifier K+ channels pass prominent inward currents, while out
ward currents are largely blocked. The inward rectification is due to
block by intracellular Mg2+ and a Mg2+-independent process described a
s intrinsic gating. The rapid loss of gating upon patch excision sugge
sts that cytoplasmic factors participate in gating. ''intrinsic'' gati
ng can be restored in excised patches by nanomolar concentrations of t
wo naturally occurring polyamines, spermine and spermidine. Spermine a
nd spermidine may function as physiological blockers of inward rectifi
er K+ channels and ''intrinsic'' gating may largely reflect voltage-de
pendent block by these cations.