Effects of cytochrome P-450 inhibitors on ionic currents in isolated rat type I carotid body cells.

Article Details

Citation

Copy to clipboard

Hatton CJ, Peers C

Effects of cytochrome P-450 inhibitors on ionic currents in isolated rat type I carotid body cells.

Am J Physiol. 1996 Jul;271(1 Pt 1):C85-92.

PubMed ID

8760033 [ View in PubMed

]

Abstract

Hypoxic chemoreception in the carotid body involves selective inhibition of K+ channels in type I cells. We have investigated whether cytochrome P-450 may act as an O2 sensor coupling hypoxia to K+ channel inhibition, by investigating the actions of P-450 inhibitors to modulate channel activity (recorded using patch-clamp techniques) in type I cells isolated from 8-to 12-day-old rat pups. The imidazole antimycotic P-450 inhibitors miconazole and clotrimazole (1-10 microM) inhibited the Ca(2+)-activated (KCa) and voltage-gated K+ (Kv) currents in isolated type I cells. Single-channel recordings indicated that the KCa channels could be inhibited directly by miconazole. Miconazole also irreversibly inhibited Ca2+ channel currents. By contrast, acute application of the suicide substrate P-450 inhibitor, 1-aminobenzotriazole (1-ABT; 3 mM) was without effect on K+ or Ca2+ currents. Hypoxia (16-23 mmHg) reversibly inhibited K+ currents and prevented the inhibitory actions of miconazole. Furthermore, the inhibitory actions of miconazole could be partially reversed by hypoxia. Pretreatment of cells for 60 min with 3 mM 1-ABT substantially reduced the inhibitory actions of hypoxia on K+ currents. Our results indicate that imidazole antimycotic P-450 inhibitors can directly and nonselectively inhibit ionic channels in type I cells but, more importantly, provide evidence to suggest that hypoxic inhibition of K+ currents in type I cells is mediated in part at least by cytochrome P-450.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Miconazole	Calcium-activated potassium channel (Protein Group)	Protein group	Humans	Unknown	Inhibitor	Details
Miconazole	Voltage-gated Potassium Channels (Protein Group)	Protein group		Unknown	Inhibitor	Details