title: Effects of osmotic changes on the chemoreceptor cell of rat carotid body.
abstract: The carotid body plays a crucial role in cardiorespiratory regulation. In the present study we investigated the effect of osmotic changes on cytoplasmic calcium concentration ([Ca(2+)](c)) and pH (pH(i)) of isolated chemoreceptor cells of the rat carotid body. In CO(2)/HCO(3)(-)-buffered medium, reduction of osmolality from the control level of 300 mosmol kg(-1) to 250-285 mosmol kg(-1) resulted in a rise in [Ca(2+)](c), as measured with Indo-1, whereas elevation of osmolality to 350 mosmol kg(-1) had no effect. The Ca(2+) response required extracellular Ca(2+) and was reduced by application of the L-type Ca(2+) channel antagonist nifedipine (10 microM). The hyposmosis-induced Ca(2+) response could be prevented by application of niflumic acid (300 microM), an inhibitor of the swelling-activated Cl(-) channel. In whole-cell patch-clamp experiments niflumic acid abolished the swelling-activated Cl(-) current but only slightly depressed the Ca(2+) current. The inhibition of Ca(2+) current by niflumic acid does not account for its action in preventing of hyposmosis-induced Ca(2+) response, which seems to be initiated by Cl(-)-mediated depolarisation. Withdrawal of CO(2)/HCO(3)(-) also prevented the Ca(2+) response. Reduction of the osmotic concentration by 50 mosmol kg(-1) induced a small but sustained decrease in pH(i), while elevation by 50 mosmol kg(-1) had an inverse effect, as measured fluorimetrically with carboxy SNARF-1. Our conclusion is that in the rat chemoreceptor cell the activation of Cl(-) channels, e.g. by hyposmotic challenge, induces depolarisation, which, in turn, activates voltage-gated Ca(2+) channels.
authors.affiliation: Department of Physiology and Laboratory of Cellular and Molecular Physiology, Semmelweis University, Faculty of Medicine, PO Box 259, H-1444 Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Molnár
authors.forename: Gábor L
authors.initials: GL
authors.lastname: Petheo
authors.forename: Csaba
authors.initials: C
authors.lastname: Fülöp
authors.forename: András
authors.initials: A
authors.lastname: Spät
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D002344:Carotid Body / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000166:cytology / Q000378:metabolism*; D018118:Chloride Channels / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004553:Electric Conductivity; D006863:Hydrogen-Ion Concentration; D009543:Nifedipine / Q000494:pharmacology; D009544:Niflumic Acid / Q000494:pharmacology; D009994:Osmolar Concentration; D009995:Osmosis; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001639:Bicarbonates; D002021:Buffers; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D018118:Chloride Channels; D002245:Carbon Dioxide; D009544:Niflumic Acid; D004533:Egtazic Acid; D009543:Nifedipine; D002118:Calcium