title: Low- and high-voltage-activated calcium channel currents and their modulation in the dorsal root ganglion cell line ND7-23.
abstract: The dorsal root ganglion-neuroblastoma cell line ND7-23 expresses low-voltage-activated calcium channel currents, and also expresses high-voltage-activated currents in about 50% of differentiated cells. Calcium channel currents were recorded with Ba2+ as the charge carrier. Low-voltage-activated currents were maximally activated at -30 mV and completely inactivated at holding potentials of -60 to -50 mV. omega-Conotoxin GVIA produced a reversible inhibition of low-voltage-activated currents, whereas the inhibition of high-voltage-activated current was largely irreversible. Dihydropyridine antagonists did not inhibit low-voltage-activated currents, whereas they inhibited a sustained, high-voltage-activated current. Low-voltage-activated currents were inhibited to a greater extent than high-voltage-activated currents by Ni2+ (100 microM) and by phenytoin (10 microM). Bradykinin (0.1 microM), baclofen (2 microM) and internal guanosine-5'-O-3-thiotriphosphate (100 microM) inhibited low-voltage-activated currents without affecting their kinetics of activation. Two classes of low-voltage-activated current were distinguished by their kinetics of inactivation. In the majority of cells, currents were slowly inactivating with a time-constant of inactivation of about 50 ms. They also exhibited a sustained component to the current, representing about 20% of the peak current. This component could be distinguished pharmacologically from high-voltage-activated current. The remainder of cells expressed a rapidly and completely inactivating current, with a time-constant of inactivation of about 20 ms. Two distinct single channel currents were observed in these cells, from cell-attached patch measurements, one had a single channel conductance of 7.9 pS, and the ensemble average current showed some inactivation. It is likely that this channel subtype underlies the low-voltage-activated current. The other showed long openings in the presence of a dihydropyridine agonist, had a conductance of 23.1 pS, and was non-inactivating.
authors.affiliation: Department of Pharmacology, Royal Free Hospital School of Medicine, London, U.K.
authors.forename: E M
authors.initials: EM
authors.lastname: Kobrinsky
authors.forename: H A
authors.initials: HA
authors.lastname: Pearson
authors.forename: A C
authors.initials: AC
authors.lastname: Dolphin
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D004095:Dihydropyridines / Q000494:pharmacology; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism; D009539:Nicotinic Acids / Q000494:pharmacology; D010069:Oxadiazoles; D010455:Peptides / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured; D020866:omega-Conotoxin GVIA
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D018377:Neurotransmitter Agents; D009539:Nicotinic Acids; D010069:Oxadiazoles; D010455:Peptides; D000643:Ammonium Chloride; C049834:PN 202-791; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010672:Phenytoin; D020866:omega-Conotoxin GVIA; D019204:GTP-Binding Proteins; D001418:Baclofen; D001920:Bradykinin