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

• Published in: The Journal of physiology Vol. 478; no. Pt 1; pp. 157 - 171
• Main Authors: Buckler, K J, Vaughan-Jones, R D
• Format: Journal Article
• Language: English
• Published: England The Physiological Society 01-07-1994
• Subjects: Action Potentials - drug effects; Animals; Calcium - metabolism; Carotid Body - physiology; Cell Hypoxia; Cell Membrane Permeability; Fura-2; Gallopamil - pharmacology; Hydrogen-Ion Concentration; In Vitro Techniques; Kinetics; Manganese - metabolism; Meglumine - pharmacology; Membrane Potentials - drug effects; Membrane Potentials - physiology; Nicardipine - pharmacology; Nickel - pharmacology; Potassium - pharmacology; Rats; Rats, Sprague-Dawley; Sodium - pharmacology; Spectrometry, Fluorescence; Strophanthidin - pharmacology; Tetrodotoxin - pharmacology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.1994.sp020239

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/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.