MILD HYPOXIA/ACIDOSIS INCREASE THE FREQUENCY OF CALCIUM OSCILLATIONS TO AUGMENT SECRETORY ACTIVITY IN RAT CAROTID BODY CHEMORECEPTORS

Abstract

In carotid body (CB) chemoreceptors (Type 1/gloms cells), severe levels of hypoxia (<1%O2) and acidosis (pH 5.0–6.5) are well known to produce strong depolarization and sustained elevation of intracellular [Ca], which enhances transmitter secretion. We studied the effects of mild and moderate levels of hypoxia (2–5%O2) and acidosis (pH7.0–7.3) on cell membrane potential (Em), Ca signaling and catecholamine secretion in Type 1 cells isolated from 3–4 week-old rats. Spontaneous Ca oscillations of varying frequency and amplitude were observed under normoxic conditions in many individual Type 1 cells in cluster. The frequency and amplitude of Ca oscillations were perfusion flow- and temperature-dependent. Verapamil (an inhibitor of both T- and L- type Ca channels), 2-APB (inhibitor of IP3 receptor and store-operated Ca entry) and removal of external Ca abolished Ca oscillations. Mild/moderate hypoxia (2–5%O2) produced low level depolarization (<12 mV) and increased the frequency and amplitude of Ca oscillations. Mild/moderate acidosis (pH 7.0–7.2) also produced small depolarization (<15 mV) and increased the frequency and amplitude of Ca oscillations. These effects of hypoxia and acidosis were reduced to varying degrees by Ca channel inhibitors, but were not inhibited by amiloride. In CB slices, both hypoxia and acidosis caused small increases in catecholamine secretion as assessed by amperometry. These findings show that mild hypoxia and acidosis increase the frequency and amplitude of Ca oscillations, thereby augmenting the secretory activity of the CB. Support or Funding Information This work was supported by funding from NIH Ca oscillations in gloms cells: effect of 2-APB This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.