Monovalent amidiniums block calcium channels in chick sensory neurons

The effect of amidiniums on high-threshold Ca2+ channel currents (ICa) was studied in chick dorsal root ganglion neurons. Guanidinium reduced ICa in a dose-dependent fashion. The block was relieved by increasing the concentration of the permeant ions, Ba2+ or Ca2+, suggesting a competition for a common binding site within the channel. Formamidinium and methyl-guanidinium suppressed ICa with similar potencies, whereas L-arginine had no effect. A neutral amidine, urea, increased ICa. In Ca(2+)-free solutions guanidinium and Na+ permeated through the Ca2+ channel equally well. Structure-activity relationship obtained for blocking efficacies of different amidiniums are used to discuss possible configurations of the selectivity filter in the Ca2+ channel.