Effect of Mild Acidosis on CA2+ Signaling in Rat Carotid Body Chemoreceptor Cells: Role of CAV, ASIC, and Task

Abstract

Carotid body (CB) glomus cells serve as peripheral chemoreceptors that detect changes in arterial O2 pressure (pO2) and pH, and adjust the level of ventilation to help maintain a normal level of blood pO2 and pH. Severe levels of hypoxia and acidosis are well known to cause sustained rise in cytosolic Ca2+ concentration ([Ca2+]c) in CB glomus cells. We showed recently that isolated gloms cells exhibit spontaneous [Ca2+]c oscillations and that mild levels of hypoxia increase the frequency and amplitude of Ca2+oscillations to augment the secretory response. To understand how mild levels of acidosis regulate Ca2+signaling in glomus cells, we studied the effects of small changes in extracellular pH (pHo) on the kinetics of Ca2+oscillations and the roles of Cav, ASIC and TASK. A decrease in pHo from 7.4 to 7.3 (mild acidosis) and 7.2 (moderate acidosis) produced significant increases in the frequency and amplitude of Ca2+ oscillations without affecting the resting basal [Ca2+]c. These effects on Ca2+ 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 Ca2+oscillations produced by mild acidosis was strongly inhibited by nifedipine (1 µM; L‐type Cav inhibitor), as well as by TTA‐P2 (20 µM; T‐type Cav inhibitor). Mild acidosis (0.1 pH unit decrease) and mild hypoxia (~5% O2) produced similar levels of change in the kinetics of Ca2+oscillations and produced an additive effect on Ca2+oscillations. Our study shows that mild to moderate levels of acidosis inhibit TASK to increase Ca2+ influx via both L‐ and T‐type Cav, resulting in increased frequency and amplitude of Ca2+ oscillations. Our study also indicate that ASICs are not involved in the stimulatory effects of mild acidosis on Ca2+oscillations.