Divalent cations: effects on post-synaptic pharmacology of invertebrate synapses.
(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) The glutamate response of the crustacean muscle was parabolically dependent 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) 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) Neither Ca++ nor Co++ depressed Cl- or K+-dependent responses coupled to the putative transmitters GABA, glutamate, dopamine or ACh. (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) 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+ conductance equally (possibly by affecting the kinetics of the mechanism).
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D003400:Astacoidea; D002118:Calcium / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D066298:In Vitro Techniques; D007478:Iontophoresis; D008274:Magnesium / Q000494:pharmacology*; D008564:Membrane Potentials; D008121:Nephropidae; D009469:Neuromuscular Junction / Q000187:drug effects*; D010424:Pentobarbital / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012908:Snails; D012964:Sodium / Q000502:physiology; D013324:Strontium / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002712:Chlorides; D005971:Glutamates; D003035:Cobalt; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D008274:Magnesium; D010424:Pentobarbital; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D004298:Dopamine; D013324:Strontium