title: Inhibition of K+ channel activity by 4-AP stimulates N-type Ca2+ channels in CHP-100 cells.
abstract: The potassium channel blocker, 4-aminopyridine (4-AP), stimulates neurotransmitter release via plasma membrane depolarization and subsequent activation of voltage-gated calcium channels. The present study assessed the effects of 4-AP on intracellular calcium levels in the human neuroblastoma cell line CHP-100. Blockade of K+ channels with 4-AP significantly increased intracellular calcium concentration ([Ca2+]i). This increase occurred via activation of plasma membrane Ca2+ channels. The 4-AP induced rise in [Ca2+]i was not inhibited by the L-type Ca2+ channel blocker nifedipine but was sensitive to the N-type Ca2+ channel blocker omega-contotoxin GVIA. Tetrodotoxin did not alter the effect of 4-AP. These results suggest that in CHP-100 cells, following inhibition of K+ channels by 4-AP, N-type Ca2+ channels are activated.
authors.affiliation: Duke University Medical Center, Division of Gastroenterology, Durham, North Carolina 27710.
authors.forename: S
authors.initials: S
authors.lastname: Basavappa
authors.forename: M A
authors.initials: MA
authors.lastname: Romano-Silva
authors.forename: A W
authors.initials: AW
authors.lastname: Mangel
authors.forename: D
authors.initials: D
authors.lastname: Laro
authors.forename: I
authors.initials: I
authors.lastname: Campbell
authors.forename: M
authors.initials: M
authors.lastname: Brammer
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012414:Rubidium Radioisotopes; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020866:omega-Conotoxin GVIA
chemical_list: D002120:Calcium Channel Agonists; D015220:Calcium Channels; D010455:Peptides; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D013779:Tetrodotoxin; D020866:omega-Conotoxin GVIA; D015761:4-Aminopyridine; D009543:Nifedipine; D002118:Calcium