Chemosensory response to high pCO is blocked by cadmium, a voltage-sensitive calcium channel blocker

In the dark, during normocapnic (pCO(2) = 35 Torr, pH(o) = 7.4) normoxia (p O(2) = 100 Torr), high pCO (> 300 Torr) causes Ca2+-dependent photolabile e xcitation of chemosensors in the carotid body (CB). We previously proposed that the source of this Ca2+ was the [Ca2+](i) stores because CO would reac t only intracellularly. However, influx of extracellular Ca2+ was not exclu ded. Now, using perfused rat CB (n = 6) in the presence of normal extracell ular [Ca2+] we show that chemosensory response to CO (pCO similar to 550 To n) in normoxic (pO(2) similar to 100 Torr) normocapnia (pCO(2) similar to 3 0 Torr, pH similar to 7.4) is completely but reversibly inhibited by Cd2+ ( 200 mu M), a voltage-gated Ca2+ channel blocker. Thus, extracellular Ca2+ i s necessary for excitatory chemosensory response to high pCO. Cd2+ block oc curs in spite of an enhanced [Ca2+](i) rise. This shows that Ca2+ rise alon e is unable to-release neurotransmitter and to elicit a chemosensory respon se. Therefore, as a corollary, we conclude that Cd2+ blocks the Ca2+ flux t hat is needed for vesicle-membrane fusion for neurotransmitter release and neural discharge. (C) 1999 Elsevier Science B.V. All rights reserved.