Effects of doxapram on ionic currents recorded in isolated type I cells of the neonatal rat carotid body.
Whole-cell patch-clamp recordings were used to investigate the effects of the respiratory stimulant doxapram on K+ and Ca2+ currents in isolated type I cells of the neonatal rat carotid body. Doxapram (1-100 microM) caused rapid, reversible and dose-dependent inhibitions of K+ currents recorded in type I cells (IC50 approximately 13 microM). Inhibition was voltage-dependent, in that the effects of doxapram were maximal at test potentials where a shoulder in the current-voltage relationship was maximal. These K+ currents were composed of both Ca(2+)-activated and Ca(2+)-independent components. Using high [Mg2+], low [Ca2+] solutions to inhibit Ca(2+)-activated K+ currents, doxapram was also seen to directly inhibit Ca(2+)-independent K+ currents. This effect was voltage-independent and was less potent (IC50 approximately 20 microM) than under control conditions, suggesting that doxapram was a more potent inhibitor of the Ca(2+)-activated K+ currents recorded under control conditions. Doxapram (10 microM) was without effect on L-type Ca2+ channel currents recorded under conditions where K+ channel activity was minimized and was also without significant effect on K+ currents recorded in the neuronal cell line NG-108 15, suggesting a selective effect on carotid body type I cells. The effects of doxapram on type I cells show similarities to those of the physiological stimuli of the carotid body, suggesting that doxapram may share a similar mechanism of action in stimulating the intact organ.
Peers
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Department of Pharmacology, Leeds University, U.K.
D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004315:Doxapram / Q000494:pharmacology*; D005910:Glioma; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats
D015220:Calcium Channels; D015221:Potassium Channels; D004315:Doxapram