Effects of caroverine and diltiazem on synaptic responses, L-glutamate-induced depolarization and potassium efflux in the frog spinal cord.
The frog spinal cord was used to determine the characteristics of the actions of caroverine and diltiazem, two organic Ca2+-antagonists, on synaptic responses and L-glutamate-induced depolarization. Caroverine and diltiazem (10(-4)M) depressed the dorsal root potential (DR-DRP) induced by electrical stimulation of an adjacent dorsal root. Diltiazem also depressed the ventral root potential (DR-VRP), whereas caroverine augmented both the polysynaptic component in the ventral root reflex and the size of the DR-VRP. The root potentials induced by high frequency stimulation (20 Hz, for 1 s) were markedly depressed by these Ca2+-antagonists at a concentration of 10(-4)M. When the preparation was perfused with normal medium, the compounds depressed L-glutamate-induced depolarizations in ventral and dorsal roots. In preparations treated with tetrodotoxin (TTX) (2 X 10(-7)M), the antagonizing actions of the drugs against L-glutamate-induced depolarizations in the ventral root were markedly reduced or abolished, while significant antagonizing actions on the depolarization in the dorsal root were still observed. The increase in extracellular K+ activity induced by L-glutamate in the TTX-treated preparation was significantly reduced by the compounds. Caroverine and diltiazem had no effect on the presynaptic nerve spike and on the focal synaptic potential induced by a single stimulation of a dorsal root; however, the focal synaptic potential induced by high frequency stimulation (20 Hz, 1 s) was attenuated. Motoneuronal action potentials were abolished by the drugs, while the excitatory postsynaptic potential remained unaffected. 9 The present results suggest that caroverine and diltiazem are not specific L-glutamate antagonists in the frog spinal cord, but that they block the initiation of an action potential without affecting presynaptic nerve conduction, transmitter release or transmitter-receptor interactions. The inhibitory effects of these compounds on L-glutamate-induced K+-efflux are discussed with reference to their Ca2+-antagonizing actions.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008839:Microelectrodes; D009046:Motor Neurons / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents; D011188:Potassium / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology*; D011892:Rana catesbeiana; D013126:Spinal Nerve Roots / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001552:Benzazepines; D005971:Glutamates; D009467:Neuromuscular Depolarizing Agents; D011810:Quinoxalines; D014665:Vasodilator Agents; D018698:Glutamic Acid; D013779:Tetrodotoxin; D004110:Diltiazem; D011188:Potassium; C000957:caroverine