Widespread depolarization during expiration: A source of respiratory drive?

Abstract

a b s t r a c tRespiration influences various pacemakers and rhythms of the body during inspiration and expiration but the underlying mechanisms are relatively unknown. Understanding this phenomenon is important, as breathing disorders, breath holding, and hyperventilation can lead to significant medical conditions. We discuss the physiological modulation of heart rhythm, blood pressure, sympathetic nerve activity, EEG, and other changes observed during inspiration and expiration. We also correlate the intracellular mitochondrial respiratory metabolic processes with real-time breathing and correlate membrane potential changes with inspiration and expiration. We propose that widespread minor hyperpolarization occurs during inspiration and widespread minor depolarization occurs during expiration. This depolarization is likely a source of respiratory drive. Further knowledge of intracellular and extracellular ionic changes associated with respiration will enhance our understanding of respiration and its role as a modulator of cellular membrane potential. This could expand treatment options for a wide range of health conditions, such as breathing disorders, stress-related disorders, and further our understanding of the Hering-Breuer reflex and respiratory sinus arrhythmia.Ó 2014 Elsevier Ltd. All rights reserved. IntroductionIn addition to gas exchange and oxygenation of the blood, respiration in the lungs can regulate multiple physiological processes throughout the body. Studies of the cardiovascular system, the peripheral nervous system, and the central nervous system provide evidence that respiratory patterns can exert a significant and immediate influence on a wide range of bodily functions, including changes in blood pressure and sympathovagal balance. Patterned respiration can regulate blood pressure and heart rate [1], as well as regulate rhythmic centers of the brain that control cardiovascular output [2,3]. While the majority of these findings have demonstrated the impact of respiration on cardiac output and other processes in isolated preparations, little work has focused on respiration's direct influence on membrane potential.This article reviews the current understanding of respiration as a regulator of cardiovascular physiology and nervous system function. More specifically, we discuss the role of respiratory rhythm and rate on both systemic and local control of these systems. We describe the role of pulmonary stretch receptors (with a focus on slowly adapting receptors) in converting breathing patterns into a functional, multi-faceted, mechanism that allows respiration to communicate with, and direct various aspects of cardiovascular and nervous system physiology. We propose a hypothesis in which inspiration and expiration are associated with transient increases and decreases in membrane potential that may underlie these widespread changes and how these membrane potential changes may underlie the chaotic dynamics of rhythmic breathing.Many studies focus on the brainstem as the primary modulator of resp...

Self-Regulation of Breathing as a Primary Treatment for Anxiety

“…In fact, the mitochondrial electron transport chain has been found to be inhibited in hypoxic placentas (Colleoni et al 2013) and oxygen and cytochrome C are limiting factors of mitochondrial respiration (Gnaiger and Kuznetsov 2002). Electron acceptors, such as oxygen, are responsible for the proton gradient and hyperpolarization that occur in the electron transport chain during mitochondrial cellular respiration (Alberts et al 2002) suggesting that fluctuations in oxygen, even minor fluctuations that occur during inspiration and expiration, may affect the degree of mitochondrial hyperpolarization and subsequently affect the rate of cellular respiration (Jerath et al 2015). Slow deep breathing, which has been shown to increase oxygenation (Bernardi et al 1998;Bilo et al 2012), may therefore lead to a slight but widespread increase in hyperpolarization of cellular membranes (Jerath et al 2015).…”

“…Electron acceptors, such as oxygen, are responsible for the proton gradient and hyperpolarization that occur in the electron transport chain during mitochondrial cellular respiration (Alberts et al 2002) suggesting that fluctuations in oxygen, even minor fluctuations that occur during inspiration and expiration, may affect the degree of mitochondrial hyperpolarization and subsequently affect the rate of cellular respiration (Jerath et al 2015). Slow deep breathing, which has been shown to increase oxygenation (Bernardi et al 1998;Bilo et al 2012), may therefore lead to a slight but widespread increase in hyperpolarization of cellular membranes (Jerath et al 2015). In addition, the existence of voltage dependent channels that transfer ions between the mitochondrial outer membrane and the cytosol (Fieni et al 2010;Kmita and Stobienia 2006) suggests that mitochondrial membrane potential changes may affect the entire cell.…”

The Dynamic Role of Breathing and Cellular Membrane Potentials in the Experience of Consciousness

“…This demonstrates that 1) respiration influences brain activity, autonomic nervous system function, blood pressure, and heart activity, and 2) respiration governs homeostatic physiology [3]. This suggests that respiratory neurons in the brainstem are vital components in respiratory control because they generate breathing activity and participate in sensory responses such as fluctuations in oxygen and carbon dioxide.…”

“…Previously it had been proposed that with inspiration the membrane potential of all cells increases, while during expiration it decreases [3]. The metabolic evidence of this correlates with ATP formation during oxygenation and decreases when oxygen availability is lower [35].…”

“…We propose that dynamic membrane potentials at the cellular level, along with their modulations by inspiration and expiration, play a fundamental role in the experience of a consciousness that is not only unified [3], but is also perceived as a living phenomenon. Western thought emphasizes that consciousness is localized in the brain; however, Eastern thought suggests that the mind and body are one, as realized, for example via meditation and Samkhya-Yoga through introspection [4].…”