Pharmacological discrimination of N-type from L-type calcium current and its selective modulation by transmitters.
GABA and norepinephrine inhibit high voltage-activated calcium current in chick sensory neurons. Using specific pharmacological tools, we have dissected this current into two components: the major one is omega-conotoxin sensitive and dihydropyridine resistant (N-type) while the minor one is dihydropyridine sensitively and omega-conotoxin resistant (L-type). The ability to selectively eliminate these two components has allowed us to determine whether the transmitters target the same or different channel types. Both GABA and norepinephrine modulate the N-type component as evidenced by their lack of effect on (1) omega-conotoxin-resistant current and (2) pure L-type tail current, prolonged by a dihydropyridine calcium channel agonist. This simple pharmacological profile will allow future tests of the significance of the two channel types in regulating sensory neuron functions.
Physiology Department, Tufts University School of Medicine, Boston, Massachusetts 02111.
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D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D004095:Dihydropyridines / Q000494:pharmacology; D004553:Electric Conductivity; D004563:Electrochemistry / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D008978:Mollusk Venoms / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008978:Mollusk Venoms; D018377:Neurotransmitter Agents; D005680:gamma-Aminobutyric Acid; D020866:omega-Conotoxin GVIA; D002118:Calcium; D009638:Norepinephrine