Effects of hypercapnia on membrane potential and intracellular calcium in rat carotid body type I cells.

An acid-induced rise in the intracellular calcium concentration (Ca2+i) of type I cells is thought to play a vital role in pH/PCO2 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 Ca(2+)-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 (approximately 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+). Ca(2+)-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.