EFFECTS OF HYPERCAPNIA ON MEMBRANE-POTENTIAL AND INTRACELLULAR CALCIUM IN RAT CAROTID-BODY TYPE-I CELLS

1. An acid-induced rise in the intracellular calcium concentration ([Ca2+](i)) of type I cells is thought to play a vital role in pH/P-CO2 chemoreception by the carotid body. In this present study we have investigated the cause of this rise in [Ca2+](i) in enzymatically isolated, neonatal rat type I cells. 2. The rise in [Ca2+](i) induced by a hypercapnic acidosis was inhibited in Ca2+-free media, and by 2 mM Ni2+. Acidosis also increased Mn2+ permeability. The rise in [Ca2+](i) is dependent, therefore, upon a Ca2+ influx from the external medium. 3. The acid-induced rise in [Ca2+](i) was attenuated by both nicardipine and methoxyverapamil (D600), suggesting a role for L-type Ca2+ channels. 4. Acidosis depolarized type I cells and often (approximate to 50 % of cells) induced action potentials. These effects coincided with a rise in [Ca2+](i). When membrane depolarization was prevented by a voltage clamp, acidosis failed to evoke a rise in [Ca2+](i). The acid-induced rise in [Ca2+](i) is a consequence, therefore, of membrane depolarization. 5. Acidosis decreased the resting membrane conductance of type I cells. The reversal potential of the acid-sensitive current was about -75 mV. 6. A depolarization (30 mM [K+](o))-induced rise in [Ca2+](i) was blocked by either the removal of extracellular Ca2+ or the presence of 2 mM Ni2+, and was also substantially inhibited by nicardipine. Under voltage-clamp conditions, [Ca2+](i) displayed a bell-shaped dependence on membrane potential. Depolarization raises [Ca2+](i), therefore, through voltage-operated Ca2+ channels. 7. Caffeine (10 mM) induced only a small rise in [Ca2+](i) (< 10 % of that induced by 30 mM extracellular K+). Ca2+-induced Ca2+ release is unlikely, therefore, to contribute greatly to the rise in [Ca2+](i) induced by depolarization. 8. Although the replacement of extracellular Na+ with N-methyl-D-glucamine (NMG), but not Li+, inhibited the acid-induced rise in [Ca2+](i), this was due to membrane hyperpolarization and not to the inhibition of Na+-Ca2+ exchange or Na+-dependent action potentials. 9. The removal of extracellular Na+ (NMG substituted) did not have a significant effect upon the resting [Ca2+](i), and only slowed [Ca2+](i) recovery slightly following repolarization from 0 to -60 mV. Therefore, if present, Na+-Ca2+ exchange plays only a minor role in [Ca2+](i) homeostasis. 10. In summary, in the neonatal rat type I cell, hypercapnic acidosis raises [Ca2+](i) through membrane depolarization and voltage-gated Ca2+ entry.