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The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells.
J Physiol. 2004 Apr 01; 556(Pt 1):175-91.JP

Abstract

Inhibitors of mitochondrial energy metabolism have long been known to be potent stimulants of the carotid body, yet their mechanism of action remains obscure. We have therefore investigated the effects of rotenone, myxothiazol, antimycin A, cyanide (CN(-)) and oligomycin on isolated carotid body type I cells. All five compounds caused a rapid rise in intracellular Ca(2+), which was inhibited on removal of extracellular Ca(2+). Under current clamp conditions rotenone and CN(-) caused a rapid membrane depolarization and elevation of [Ca(2+)](i). Voltage clamping cells to -70 mV substantially attenuated this rise in [Ca(2+)](i). Rotenone, cyanide, myxothiazol and oligomycin significantly inhibited resting background K(+) currents. Thus rotenone, myxothiazol, cyanide and oligomycin mimic the effects of hypoxia in that they all inhibit background K(+) current leading to membrane depolarization and voltage-gated calcium entry. Hypoxia, however, failed to have any additional effect upon membrane currents in the presence of CN(-) or rotenone or the mitochondrial uncoupler p-trifluoromethoxyphenyl hydrazone (FCCP). Thus not only do mitochondrial inhibitors mimic the effects of hypoxia, but they also abolish oxygen sensitivity. These observations suggest that there is a close link between oxygen sensing and mitochondrial function in type I cells. Mechanisms that could account for this link and the actions of mitochondrial inhibitors are discussed.

Authors+Show Affiliations

University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14724184

Citation

Wyatt, C N., and K J. Buckler. "The Effect of Mitochondrial Inhibitors On Membrane Currents in Isolated Neonatal Rat Carotid Body Type I Cells." The Journal of Physiology, vol. 556, no. Pt 1, 2004, pp. 175-91.
Wyatt CN, Buckler KJ. The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells. J Physiol. 2004;556(Pt 1):175-91.
Wyatt, C. N., & Buckler, K. J. (2004). The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells. The Journal of Physiology, 556(Pt 1), 175-91.
Wyatt CN, Buckler KJ. The Effect of Mitochondrial Inhibitors On Membrane Currents in Isolated Neonatal Rat Carotid Body Type I Cells. J Physiol. 2004 Apr 1;556(Pt 1):175-91. PubMed PMID: 14724184.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells. AU - Wyatt,C N, AU - Buckler,K J, Y1 - 2004/01/14/ PY - 2004/1/16/pubmed PY - 2004/11/13/medline PY - 2004/1/16/entrez SP - 175 EP - 91 JF - The Journal of physiology JO - J Physiol VL - 556 IS - Pt 1 N2 - Inhibitors of mitochondrial energy metabolism have long been known to be potent stimulants of the carotid body, yet their mechanism of action remains obscure. We have therefore investigated the effects of rotenone, myxothiazol, antimycin A, cyanide (CN(-)) and oligomycin on isolated carotid body type I cells. All five compounds caused a rapid rise in intracellular Ca(2+), which was inhibited on removal of extracellular Ca(2+). Under current clamp conditions rotenone and CN(-) caused a rapid membrane depolarization and elevation of [Ca(2+)](i). Voltage clamping cells to -70 mV substantially attenuated this rise in [Ca(2+)](i). Rotenone, cyanide, myxothiazol and oligomycin significantly inhibited resting background K(+) currents. Thus rotenone, myxothiazol, cyanide and oligomycin mimic the effects of hypoxia in that they all inhibit background K(+) current leading to membrane depolarization and voltage-gated calcium entry. Hypoxia, however, failed to have any additional effect upon membrane currents in the presence of CN(-) or rotenone or the mitochondrial uncoupler p-trifluoromethoxyphenyl hydrazone (FCCP). Thus not only do mitochondrial inhibitors mimic the effects of hypoxia, but they also abolish oxygen sensitivity. These observations suggest that there is a close link between oxygen sensing and mitochondrial function in type I cells. Mechanisms that could account for this link and the actions of mitochondrial inhibitors are discussed. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/14724184/The_effect_of_mitochondrial_inhibitors_on_membrane_currents_in_isolated_neonatal_rat_carotid_body_type_I_cells_ L2 - https://doi.org/10.1113/jphysiol.2003.058131 DB - PRIME DP - Unbound Medicine ER -