Acid‐evoked quantal catecholamine secretion from rat phaeochromocytoma cells and its interaction with hypoxia‐evoked secretion

Abstract

The carotid body is the major arterial chemoreceptor and responds to physiological stimuli (hypoxia, hypercapnia, acidosis) by increasing the discharge frequency of afferent chemosensory neurons, thereby initiating corrective changes in breathing pattern (Fidone & Gonzalez, 1986;Gonzalez et al. 1994). Type I (glomus) cells within the carotid body are central to this chemoreceptive process, releasing transmitters -particularly catecholamines -in response to physiological stimuli in a manner which correlates well with increased chemosensory nerve activity (reviewed by Gonzalez et al. 1994). Patch-clamp recordings have shown that type I cells possess Oµ-sensitive K¤ channels whose activity is reduced under hypoxic conditions (Lopez-Barneo et al. 1988;Delpiano & Hescheler, 1989;Peers, 1990a;Stea & Nurse, 1991). Such an effect causes membrane depolarization, opening of voltage-gated Ca¥ channels (Buckler & Vaughan-Jones, 1994a;Wyatt & Peers, 1995) and thus transmitter release (Urena et al. 1994). In the rat model, evidence suggests that acidicÏhypercapnic stimuli evoke transmitter release via a similar mechanism (Peers, 1990b;Peers & Green, 1991; Buckler & Vaughan-Jones, 1994b) although in the rabbit model, a completely different mechanism has been put forward to account for transduction of acidic stimuli (Rocher et al. 1991). Hypoxic and acidic stimuli are well-known to be multiplicative in their ability to increase afferent chemosensory nerve discharge (Fitzgerald & Parks, 1971;Lahiri & Delaney, 1975), an effect which may account for the well-known postnatal maturation of this sensory organ (Pepper et al. 1995). However, no explanation has been forwarded to account for this interactive effect at the cellular level, and it remains unknown whether this interaction occurs within the type I cell or involves other cellular elements of the carotid body. Recently, evidence has emerged that the rat phaeochromocytoma (PC12) cell line responds to hypoxia in a manner which is remarkably similar to that of the type I carotid body cell. Thus, hypoxia inhibits K¤ channels in these cells, causing membrane depolarization and a subsequent rise in [Ca¥]é (Zhu et al. 1996;Conforti & Millhorn, 1997). In addition, we have shown that hypoxia evokes quantal secretion of catecholamines from PC12 cells, which is entirely dependent on Ca¥ influx through voltage-

Hypoxia and acidosis increase the secretion of catecholamines in the neonatal rat adrenal medulla: an in vitro study

“…These results imply that in the neonatal AM, Ͼ85% of the acidic secretory response is dependent on extracellular Ca 2ϩ as is the case in the adult CB (28,32) and in rat pheochromocytoma (PC)-12 cells (a cell line derived from rat AM pheochromocytomas sensitive to hypoxia; see Ref. 41). Similar Ca 2ϩ dependence was demonstrated recently for isohydric hypercapnia in neonatal rat tissue slices (27).…”

Prediction of Local pH Variations during Amperometric Monitoring of Vesicular Exocytotic Events at Chromaffin Cells

“…This shows that the changes reported after acidifying or basifying the extracellular medium represent-most certainly-changes in the frequency and intensity of the successive exocytotic events due to intracellular changes incurred by the cells before the actual amperometric measurements were performed while the cell was exposed to such acidic or basic buffer. [33][34][35][36][37] …”

“…In the following we wish to investigate this from a physicochemical point of view, though it is not our purpose here to presuppose that this may lead to any significant effects on the biological phenomenon investigated. It must, nevertheless, be emphasized in this context that several reports have produced evidences that modifying the extracellular pH altered exocytosis at chromaffin cells (adrenaline and/or nor-adrenaline), [33,34] PC12 cells (dopamine), [35] and pancreatic b-cells (serotonin and insulin). [36,37] Yet, the analysis presented below indicates that the interpretation of such data is not as straightforward as it may seem.…”

Rat Adrenal Chromaffin Cells Are Neonatal CO2Sensors

“…Calcium requirements for secretion in bovine chromaffin cells have been extensively studied (Augustine and Neher, 1992). In other catecholaminergic secretory cells, such as rabbit (Ureña et al, 1994) and rat (Pardal et al, 2000) carotid body glomus cells or PC12 cells (Taylor et al, 1999), the secretory response to hypoxia has also been shown to depend on extracellular Ca 2ϩ influx. A, Amperometric recording of a neonatal chromaffin cell from an adrenal gland slice illustrating the secretory activity evoked by increasing CO 2 levels from control (5%) to hypercapnia (10 and 20%).…”