Chemosensory response to high pCO is blocked by cadmium, a voltage-sensitive calcium channel blocker.
In the dark, during normocapnic (pCO2=35 Torr, pHo=7.4) normoxia (pO2=100 Torr), high pCO (>300 Torr) causes Ca2+-dependent photolabile excitation of chemosensors in the carotid body (CB). We previously proposed that the source of this Ca2+ was the [Ca2+]i stores because CO would react only intracellularly. However, influx of extracellular Ca2+ was not excluded. Now, using perfused rat CB (n=6) in the presence of normal extracellular [Ca2+] we show that chemosensory response to CO (pCO approximately 550 Torr) in normoxic (pO2 approximately 100 Torr) normocapnia (pCO2 approximately 30 Torr, pH approximately 7.4) is completely but reversibly inhibited by Cd2+ (200 microM), a voltage-gated Ca2+ channel blocker. Thus, extracellular Ca2+ is necessary for excitatory chemosensory response to high pCO. Cd2+ block occurs in spite of an enhanced [Ca2+]i rise. This shows that Ca2+ rise alone is unable to release neurotransmitter and to elicit a chemosensory response. Therefore, as a corollary, we conclude that Cd2+ blocks the Ca2+ flux that is needed for vesicle-membrane fusion for neurotransmitter release and neural discharge.
Rozanov
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Department of Physiology, University of Pennsylvania Medical Center, B400 Richards Building, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
Roy
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Mokashi
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A
Wilson
D F
DF
Lahiri
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S
Acker
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H
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D020864:Calcium Channels, N-Type; D002248:Carbon Monoxide / Q000378:metabolism*; D002344:Carotid Body / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000187:drug effects* / Q000502:physiology*; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D010313:Partial Pressure; D010775:Photic Stimulation; D051381:Rats
D002104:Cadmium; D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D002248:Carbon Monoxide