Effects of aerobic and anaerobic metabolic inhibitors on avian intrapulmonary chemoreceptors

Abstract

Birds have rapidly responding respiratory chemoreceptors [intrapulmonary chemoreceptors (IPC)] that provide vagal sensory feedback about breathing pattern. IPC are exquisitely sensitive to CO(2) but are unaffected by hypoxia. IPC continue to respond to CO(2) during hypoxic and even anoxic conditions, suggesting that they may generate ATP needed for signal transduction anaerobically. To assess IPC energy metabolism, single-cell action potential discharge and acid-base status were recorded from 26 pentobarbital-anesthetized Anas platyrhynchos before and after intravenous infusion of the glycolytic blocker iodoacetate (10-70 mg/kg), mitochondrial blocker rotenone (2 mg/kg), and/or mitochondrial uncoupler 2,4-dinitrophenol (5-15 mg/kg). After 5 min exposure at the highest dosages, iodoacetate inhibited IPC discharge 65% (15.9 +/- 0.3 s(-1) to 5.5 +/- 0.3 s(-1), P < 0.05), rotenone inhibited discharge 80% (12.9 +/- 0.5 s(-1) to 2.6 +/- 0.6 s(-1), P < 0.05), and 2,4-dinitrophenol inhibited discharge 19% (14.0 +/- 0.3 s(-1) to 11.3 +/- 0.3 s(-1), P < 0.05). These results suggest that IPC utilize glucose, require an intact glycolytic pathway, and metabolize the products of glycolysis to CO(2) and H(2)O by mitochondrial respiration. The small but significant effect of 2,4-dinitrophenol suggests that ATP production by glycolysis may be sufficient to meet IPC energy demands if NADH can be oxidized to NAD experimentally by uncoupling mitochondria, or physiologically by transient lactate production. A model for IPC spike frequency adaptation is proposed, whereby the rapid onset of phasic IPC discharge requires ATP from anaerobic glycolysis, using lactate as the electron acceptor, and the roll-off in IPC discharge reflects transient acidosis due to intracellular lactic acid accumulation.

Coping with extremes: lowered myocardial phosphofructokinase activities and glucose content but increased fatty acids content in highland Eurasian Tree Sparrows

“…We detected both highland and lowland sparrows had similar maximal LDH and CK activities, which means similar maximal velocity on lactate metabolism for both populations. There are two possible explanations: (1) highland sparrows are able to counter the adverse effect of anaerobic metabolism, which is more easily induced by hypoxic environment (Samaja et al 1997;Pilarski et al 2009), on acid-base equilibrium in cardiomyocytes via lower glycolysis level (Burggren and Cameron 1980;Casiday and Frey 2012;Hebisz et al 2016) ; (2) both population possessed similar maximal capacity on production and regeneration of ATP by lactate metabolism (Ingwall et al 1985;Kodde et al 2007), which indicate that the highland sparrows, compared to their lowland counterparts, could better cope with the extra demand of ATP when the cardiac workloads increased but the aerobic metabolism is suppressed. Since the leakage of LDH and CK into the cardiovascular system are documented as indexes of myocardial injury (Kaur et al 1997), our results showed that the cardiac functions of both the highland and lowland sparrows were unlikely to be injured.…”