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-mu-M) caused rapid, reversible and dose-dependent inhibitions of K+ currents recorded in type I cells (IC50 approximately 13-mu-M). 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 Ca2+-activated and Ca2+-independent components. Using high [Mg2+], low [Ca2+] solutions to inhibit Ca2+-activated K+ currents, doxapram was also seen to directly inhibit Ca2+-independent K+ currents. This effect was voltage-independent and was less potent (IC50 approximately 20-mu-M) than under control conditions, suggesting that doxapram was a more potent inhibitor of the Ca2+-activated K+ currents recorded under control conditions. Doxapram (10-mu-M) 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.