title: Augmentation of calcium current by hypoxia in carotid body glomus cells.
abstract: Several lines of evidence indicate that transduction of the hypoxic stimulus at the carotid body involves an increase in cytosolic Ca2+ ([Ca2+]i) via activation of voltage-gated Ca2+ channels in the glomus cells. However, reported responses to hypoxia include either no effect on or inhibition of Ca2+ current in glomus cells. The apparent discrepancy between the effects of hypoxia on [Ca2+]i and Ca2+ channel activity prompted us to re-examine the effects of low oxygen on Ca2+ currents in glomus cells. Experiments were performed on freshly dissociated glomus cells from rabbit carotid bodies. Ca2+ channel activity was monitored using the whole-cell configuration of the patch clamp technique with Ba2+ as the charge carrier. Hypoxia (pO2 = 40 mmHg) augmented the Ca2+ current by 24% (at 0 mV). This augmentation was seen in a CO2/HCO3- but not in a HEPES buffered extracellular solution. However, when the extracellular pH (pHo) of a HEPES buffered solution is lowered from 7.4 to 7.0, then the Ca2+ current in glomus cells is augmented by hypoxia by 20%. Nisoldipine, an L-type Ca2+ channel blocker (2 microM), prevented augmentation of the Ca2+ current by hypoxia. On the other hand, an N- and P-type Ca2+ channel blocker (2 microM omega-conotoxin MVIIC) did not prevent the augmentation of the Ca2+ current by hypoxia. Protein kinase C (PKC) inhibitors, staurosporine (100 nM) and bisindolylmaleimide (2 microM), prevented augmentation by hypoxia. Okadaic acid (100 nM), an inhibitor of serine/threonine phosphatases also prevented augmentation of Ca2+ current by hypoxia; whereas, norokadaone, an inactive analog of okadaic acid, had no effect. These results suggest that hypoxia augments Ca2+ current through L-type Ca2+ channels via a PKC and/or phosphatase-sensitive pathways.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Summers
authors.forename: J L
authors.initials: JL
authors.lastname: Overholt
authors.forename: N R
authors.initials: NR
authors.lastname: Prabhakar
mesh_terms: D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials; D015737:Nisoldipine / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D002021:Buffers; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D019319:Okadaic Acid; D015737:Nisoldipine; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D019311:Staurosporine; C088060:bisindolylmaleimide; D002118:Calcium