Blockade by neurotransmitter antagonists of veratridine-activated ion channels in neuronal cell lines.
The voltage-dependent Na+ ionophore of various neuronal cells is permeable not only to Na+ ions but also to guanidinium ions. Therefore, the veratridine- (or aconitine-)stimulated influx of [14C]guanidinium in neuroblastoma x glioma hybrid cells was measured to characterize the Na+ ionophore of these cells. Half-maximal stimulation of guanidinium uptake was seen at 30 microM veratridine. At 1 mM guanidinium, the veratridine-stimulated uptake of guanidinium was lowered to 50% by approximately 60 mM Li+, Na+, or K+ and by a few millimolar Mn2+, Co2+, or Ni2+. The basal, as well as the veratridine-stimulated, uptake of guanidinium was inhibited by the cholinergic antagonists (+)-tubocurarine (Ki = 50 to 500 nM) and atropine (Ki = 5 to 30 microM) and the adrenergic antagonists phentolamine (Ki = 5 microM) and propranolol (Ki = 60 microM). The specificity of the inhibitory effects of these agents is stressed by the ineffectiveness of various other neurotransmitter antagonists. However, the corresponding ionophore in neuroblastoma cells (clone N1E-115) seems to be regulated differently. While phentolamine and propranolol inhibit the veratridine-activated uptake as in the hybrid cells, (+)-tubocurarine and atropine exert only a slight effect.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005910:Glioma / Q000503:physiopathology*; D019791:Guanidine; D006146:Guanidines / Q000378:metabolism; D006822:Hybrid Cells / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D014403:Tubocurarine / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
D006146:Guanidines; D007473:Ion Channels; D018377:Neurotransmitter Agents; D014701:Veratridine; D001285:Atropine; D011433:Propranolol; D014702:Veratrine; D019791:Guanidine; D002118:Calcium; D014403:Tubocurarine; D010646:Phentolamine