Monovalent amidiniums block calcium channels in chick sensory neurons

The effect of amidiniums on high-threshold Ca²⁺ channel currents (I _Ca) was studied in chick dorsal root ganglion neurons. Guanidinium reduced I _Ca 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 I _Ca with similar potencies, whereas l-arginine had no effect. A neutral amidine, urea, increased I _Ca. In Ca²⁺-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.The author wishes to thank Ms. S. Engers for the cell isolation and making of the electrodes.