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Effect of Mild Acidosis on CA 2+ Signaling in Rat Carotid Body Chemoreceptor Cells: Role of CAV, ASIC, and Task
Author(s) -
Kim Donghee,
Hogan James O.,
White Carl
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r2543
Subject(s) - acidosis , glomus cell , carotid body , nifedipine , extracellular , hypoxia (environmental) , endocrinology , medicine , chemoreceptor , intracellular ph , chemistry , amiloride , calcium , biology , biochemistry , receptor , oxygen , sodium , stimulation , organic chemistry
Carotid body (CB) glomus cells serve as peripheral chemoreceptors that detect changes in arterial O 2 pressure (pO 2 ) and pH, and adjust the level of ventilation to help maintain a normal level of blood pO 2 and pH. Severe levels of hypoxia and acidosis are well known to cause sustained rise in cytosolic Ca 2+ concentration ([Ca 2+ ] c ) in CB glomus cells. We showed recently that isolated gloms cells exhibit spontaneous [Ca 2+ ] c oscillations and that mild levels of hypoxia increase the frequency and amplitude of Ca 2+ oscillations to augment the secretory response. To understand how mild levels of acidosis regulate Ca 2+ signaling in glomus cells, we studied the effects of small changes in extracellular pH (pH o ) on the kinetics of Ca 2+ oscillations and the roles of Ca v , ASIC and TASK. A decrease in pH o from 7.4 to 7.3 (mild acidosis) and 7.2 (moderate acidosis) produced significant increases in the frequency and amplitude of Ca 2+ oscillations without affecting the resting basal [Ca 2+ ] c . These effects on Ca 2+ oscillations were not blocked by 0.1 mM amiloride (an ASIC inhibitor) that blocked Na‐H exchange in glomus cells. Mild acidosis was associated with a small but significant inhibition of TASK current and cell depolarization. The increase in Ca 2+ oscillations produced by mild acidosis was strongly inhibited by nifedipine (1 µM; L‐type Ca v inhibitor), as well as by TTA‐P2 (20 µM; T‐type Ca v inhibitor). Mild acidosis (0.1 pH unit decrease) and mild hypoxia (~5% O 2 ) produced similar levels of change in the kinetics of Ca 2+ oscillations and produced an additive effect on Ca 2+ oscillations. Our study shows that mild to moderate levels of acidosis inhibit TASK to increase Ca 2+ influx via both L‐ and T‐type Ca v , resulting in increased frequency and amplitude of Ca 2+ oscillations. Our study also indicate that ASICs are not involved in the stimulatory effects of mild acidosis on Ca 2+ oscillations.