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.
Cox
D H
DH
Physiology Department, Tufts University School of Medicine, Boston, Massachusetts 02111.
Dunlap
K
K
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