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.
Mironov
S L
SL
Max-Planck-Institute for Psychiatry, Planegg-Martinsried, Germany.
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D002645:Chickens; D005727:Ganglia, Spinal / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014508:Urea / Q000494:pharmacology
D000578:Amidines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D006146:Guanidines; D001464:Barium; C077922:formamidine; D014508:Urea; D001120:Arginine; D012964:Sodium; D005947:Glucose; D019791:Guanidine