Tricyclic antidepressants inhibit Ca(2+)-activated K(+)-efflux in cultured spinal cord neurons.
The effect of tricyclic antidepressants and monoamine oxidase inhibotors on the Ca(2+)-activated K(+)-efflux was studied using 86Rb-efflux assay in primary cultured mouse spinal cord neurons. Depolarization of the cultured cells with 100 mM KCl increased the 86Rb-efflux significantly in Ca(2+)-containing buffer, but not in Ca(2+)-free buffer. All the antidepressants examined, except the monoamine oxidase inhibitors, inhibited the 86Rb-efflux. Desipramine exhibited additivity with tetraethyl ammonium (TEA) and quinine sulfate (QSO4), but not with GABAB receptor agonist baclofen. The inhibitory action of antidepressants was not mediated through the GABAB receptors, since GABAB receptor antagonist, phaclofen, was unable to antagonize this effect. The ability of tricyclic antidepressants to inhibit calcium ionophore (A 23187)-induced 86Rb-efflux suggests that these drugs do not act at the level of voltage-gated Ca(2+)-channels. Furthermore, this effect does not seem to involve the G-proteins, adenylate cyclase, or protein kinase C systems, since pertussis toxin (PTX) and the activators of adenylate cyclase and protein kinase C did not reverse the effect of tricyclics on 86Rb-efflux. Taken together, these results suggest that antidepressants inhibit Ca(2+)-activated K(+)-channels at a stage subsequent to the voltage-gated Ca(2+)-channels.
Kamatchi
G L
GL
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
Ticku
M K
MK
D037361:Adenylate Cyclase Toxin; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004622:Embryo, Mammalian; D005260:Female; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012413:Rubidium / Q000378:metabolism; D013116:Spinal Cord / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000929:Antidepressive Agents, Tricyclic; D015221:Potassium Channels; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin; D037342:Pertussis Toxin; D012413:Rubidium; D011188:Potassium; D002118:Calcium; D003891:Desipramine