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 ([Ca2+]c) and pH (pHi) of isolated chemoreceptor cells of the rat carotid body. In CO2/HCO3--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 [Ca2+]c, as measured with Indo-1, whereas elevation of osmolality to 350 mosmol kg-1 had no effect. The Ca2+ response required extracellular Ca2+ and was reduced by application of the L-type Ca2+ channel antagonist nifedipine (10 μM). The hyposmosis-induced Ca2+ response could be prevented by application of niflumic acid (300 μM), 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 Ca2+ current. The inhibition of Ca2+ current by niflumic acid does not account for its action in preventing of hyposmosis-induced Ca2+ response, which seems to be initiated by Cl--mediated depolarisation. Withdrawal of CO2/HCO3- also prevented the Ca2+ response. Reduction of the osmotic concentration by 50 mosmol kg-1 induced a small but sustained decrease in pHi, 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 Ca2+ channels.
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