Divalent cations: effects on post-synaptic pharmacology of invertebrate synapses

Abstract

1. (1) The effects of divalent cations (Ca ++, Mg ++, Sr ++ and Co ++) were studied on the post-synaptic responses of crustacean neuromuscular junctions and identified molluscan neurons to bath and iontophoretic application of putative transmitters. 2. (2) The glutamate response of the crustacean muscle was parabolically dependent o on [Ca ++] 0, while the ACh response of an identified molluscan neuron was inversely dependent on [Ca ++] 0. Elevated [Ca ++] 0 depressed both glutamate and ACh depolarizations in a concentration-dependent, reversible manner. Low concentrations of Co ++ also depressed both depolarizations in a concentration-dependent, reversible manner. 3. (3) Double-reciprocal plot analyses of the Ca ++ and Co ++ depressions indicate that these agents were apparently not acting to reduce the affinity of the receptor for the agonist. Elevated concentrations of both Ca ++ and Co ++ shifted the inversion potential of the ACh response in a hyperpolarizing direction, suggesting a preferential block of the receptor-coupled Na + conductance. 4. (4) Neither Ca ++ nor Co ++ depressed Cl −- or K +-dependent responses coupled to the putative transmitters GABA, glutamate, dopamine or ACh. 5. (5) The selective inhibition of the ACh and glutamate responses by the general anesthetic pentobarbital was examined as a function of [Ca ++] 0. Decreasing [Ca ++ 0 by 5-fold decreased the pentobarbital inhibition by about 50% while increasing [Ca ++] 0 by 5-fold produced an insignificant increase in the inhibition. 6. (6) The data indicate that divalent cations, like general anesthetics, selectively depress post-synaptic excitatory responses that are primarily Na +-dependent. This selective depression by Ca ++ could contribute to its anesthetic and anticonvulsant properties when present in elevated concentrations in the ventricular fluid. The mechanism by which divalent ions and general anesthetics selectively depress receptor-coupled conductances appear to be different: divalent ions preferentially attack the Na + component while anesthetics block Na + and K + conductances equally (possibly by affecting the kinetics of the mechanism).