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Annual Review of Physiology 2015Lysosomes are acidic compartments filled with more than 60 different types of hydrolases. They mediate the degradation of extracellular particles from endocytosis and of... (Review)
Review
Lysosomes are acidic compartments filled with more than 60 different types of hydrolases. They mediate the degradation of extracellular particles from endocytosis and of intracellular components from autophagy. The digested products are transported out of the lysosome via specific catabolite exporters or via vesicular membrane trafficking. Lysosomes also contain more than 50 membrane proteins and are equipped with the machinery to sense nutrient availability, which determines the distribution, number, size, and activity of lysosomes to control the specificity of cargo flux and timing (the initiation and termination) of degradation. Defects in degradation, export, or trafficking result in lysosomal dysfunction and lysosomal storage diseases (LSDs). Lysosomal channels and transporters mediate ion flux across perimeter membranes to regulate lysosomal ion homeostasis, membrane potential, catabolite export, membrane trafficking, and nutrient sensing. Dysregulation of lysosomal channels underlies the pathogenesis of many LSDs and possibly that of metabolic and common neurodegenerative diseases.
Topics: Animals; Exocytosis; Homeostasis; Humans; Ion Channels; Ions; Lysosomal Storage Diseases; Lysosomes; Membrane Potentials
PubMed: 25668017
DOI: 10.1146/annurev-physiol-021014-071649 -
Sensors (Basel, Switzerland) Feb 2021Brain functions are fundamental for the survival of organisms, and they are supported by neural circuits consisting of a variety of neurons. To investigate the function... (Review)
Review
Brain functions are fundamental for the survival of organisms, and they are supported by neural circuits consisting of a variety of neurons. To investigate the function of neurons at the single-cell level, researchers often use whole-cell patch-clamp recording techniques. These techniques enable us to record membrane potentials (including action potentials) of individual neurons of not only anesthetized but also actively behaving animals. This whole-cell recording method enables us to reveal how neuronal activities support brain function at the single-cell level. In this review, we introduce previous studies using in vivo patch-clamp recording techniques and recent findings primarily regarding neuronal activities in the hippocampus for behavioral function. We further discuss how we can bridge the gap between electrophysiology and biochemistry.
Topics: Action Potentials; Animals; Hippocampus; Membrane Potentials; Neurons; Patch-Clamp Techniques
PubMed: 33669656
DOI: 10.3390/s21041448 -
Physiological Reviews Jan 2024Cell excitability and its modulation by hormones and neurotransmitters involve the concerted action of a large repertoire of membrane proteins, especially ion channels.... (Review)
Review
Cell excitability and its modulation by hormones and neurotransmitters involve the concerted action of a large repertoire of membrane proteins, especially ion channels. Unique complements of coexpressed ion channels are exquisitely balanced against each other in different excitable cell types, establishing distinct electrical properties that are tailored for diverse physiological contributions, and dysfunction of any component may induce a disease state. A crucial parameter controlling cell excitability is the resting membrane potential (RMP) set by extra- and intracellular concentrations of ions, mainly Na, K, and Cl, and their passive permeation across the cell membrane through leak ion channels. Indeed, dysregulation of RMP causes significant effects on cellular excitability. This review describes the molecular and physiological properties of the Na leak channel NALCN, which associates with its accessory subunits UNC-79, UNC-80, and NLF-1/FAM155 to conduct depolarizing background Na currents in various excitable cell types, especially neurons. Studies of animal models clearly demonstrate that NALCN contributes to fundamental physiological processes in the nervous system including the control of respiratory rhythm, circadian rhythm, sleep, and locomotor behavior. Furthermore, dysfunction of NALCN and its subunits is associated with severe pathological states in humans. The critical involvement of NALCN in physiology is now well established, but its study has been hampered by the lack of specific drugs that can block or agonize NALCN currents in vitro and in vivo. Molecular tools and animal models are now available to accelerate our understanding of how NALCN contributes to key physiological functions and the development of novel therapies for NALCN channelopathies.
Topics: Humans; Animals; Sodium Channels; Ion Channels; Membrane Potentials; Neurons; Sodium; Membrane Proteins
PubMed: 37615954
DOI: 10.1152/physrev.00014.2022 -
Channels (Austin, Tex.) Mar 2017Ion channels constitute a superfamily of membrane proteins found in all living creatures. Their activity allows fast translocation of ions across the plasma membrane... (Review)
Review
Ion channels constitute a superfamily of membrane proteins found in all living creatures. Their activity allows fast translocation of ions across the plasma membrane down the ion's transmembrane electrochemical gradient, resulting in a difference in electrical potential across the plasma membrane, known as the membrane potential. A group within this superfamily, namely voltage-gated channels, displays activity that is sensitive to the membrane potential. The activity of voltage-gated channels is controlled by the membrane potential, while the membrane potential is changed by these channels' activity. This interplay produces variations in the membrane potential that have evolved into electrical signals in many organisms. These signals are essential for numerous biological processes, including neuronal activity, insulin release, muscle contraction, fertilization and many others. In recent years, the activity of the voltage-gated channels has been observed not to follow a simple relationship with the membrane potential. Instead, it has been shown that the activity of voltage-gated channel displays hysteresis. In fact, a growing number of evidence have demonstrated that the voltage dependence of channel activity is dynamically modulated by activity itself. In spite of the great impact that this property can have on electrical signaling, hysteresis in voltage-gated channels is often overlooked. Addressing this issue, this review provides examples of voltage-gated ion channels displaying hysteretic behavior. Further, this review will discuss how Dynamic Voltage Dependence in voltage-gated channels can have a physiological role in electrical signaling. Furthermore, this review will elaborate on the current thoughts on the mechanism underlying hysteresis in voltage-gated channels.
Topics: Animals; Humans; Ion Channels; Membrane Potentials; Models, Biological; Signal Transduction; Thermodynamics
PubMed: 27689426
DOI: 10.1080/19336950.2016.1243190 -
Advances in Physiology Education Dec 2015From a Cartesian perspective of rational analysis, the electric potential difference across the cell membrane is one of the fundamental concepts for the study of...
From a Cartesian perspective of rational analysis, the electric potential difference across the cell membrane is one of the fundamental concepts for the study of physiology. Unfortunately, undergraduate students often struggle to understand the genesis of this energy gradient, which makes the teaching activity a hard task for the instructor. The topic of bioelectrogenesis encompasses multidisciplinary concepts, involves several mechanisms, and is a dynamic process, i.e., it never turns off during the lifetime of the cell. Therefore, to improve the transmission and acquisition of knowledge in this field, I present an alternative didactic model. The design of the model assumes that it is possible to build, in a series of sequential steps, an assembly of proteins within the membrane of an isolated cell in a simulated electrophysiology experiment. Initially, no proteins are inserted in the membrane and the cell is at a baseline energy state; the extracellular and intracellular fluids are at thermodynamic equilibrium. Students are guided through a sequence of four steps that add key membrane transport proteins to the model cell. The model is simple at the start and becomes progressively more complex, finally producing transmembrane chemical and electrical gradients. I believe that this didactic approach helps instructors with a more efficient tool for the teaching of the mechanisms of resting membrane potential while helping students avoid common difficulties that may be encountered when learning this topic.
Topics: Animals; Biological Transport; Cell Membrane Permeability; Comprehension; Curriculum; Education, Professional; Electric Conductivity; Humans; Learning; Membrane Potentials; Models, Biological; Physiology; Students; Teaching; Thermodynamics
PubMed: 26628666
DOI: 10.1152/advan.00051.2015 -
Advances in Physiology Education Mar 2021University-level physiology courses are considered challenging. Postsecondary instructors indicate the top three reasons that make physiology courses difficult for...
University-level physiology courses are considered challenging. Postsecondary instructors indicate the top three reasons that make physiology courses difficult for student are ) the need for the learner to reason mechanistically, ) the belief among students that memorization is equal to learning, and ) the need to think about the physiological systems as dynamic systems. One topic that encompasses all three aforementioned challenges is membrane potential and its determinants in living organisms. Membrane potential is the mechanism that underlies numerous physiological processes; memorization of these processes does not equate to understanding, and its very nature is highly dynamic. Unfortunately, students find the topic challenging, and even students who have learned and practiced the topic in previous terms, fail to retain the conceptual understanding of the underlying mechanisms. Importantly, understanding many systemic physiological processes relies on students' mastery of concepts related to membrane potential. Stephan H. Wright rightfully wrote that "It would be difficult to exaggerate the physiological significance of [membrane potential]". Therefore, to more effectively facilitate students' learning of additional topics, educators must ensure that students can build on, understand, and appreciate the complexities of membrane potential determination. This article presents a tool to aid instructors of all level in teaching the topic of membrane potential.
Topics: Humans; Learning; Membrane Potentials; Physiological Phenomena; Students; Teaching; Universities
PubMed: 33529144
DOI: 10.1152/advan.00174.2020 -
Invertebrate Neuroscience : IN Nov 2018Na/K-pump is an electrogenic transmembrane ATPase located in the outer plasma membrane of cells. The Na/K-ATPase pumps 3 sodium ions out of cells while pumping 2... (Review)
Review
Na/K-pump is an electrogenic transmembrane ATPase located in the outer plasma membrane of cells. The Na/K-ATPase pumps 3 sodium ions out of cells while pumping 2 potassium ions into cells. Both cations move against their concentration gradients. This enzyme's electrogenic nature means that it has a chronic role in stabilizing the resting membrane potential of the cell, in regulating the cell volume and in the signal transduction of the cell. This review will mainly consider the role of the Na/K-pump in neurons, with an emphasis on its role in modulating neurotransmitter receptor. Most of the literature on the modulation of neurotransmitter receptors refers to the situation in the mammalian nervous system, but the position is likely to be similar in most, if not all, invertebrate nervous systems.
Topics: Animals; Humans; Membrane Potentials; Neurons; Receptors, Neurotransmitter; Sodium-Potassium-Exchanging ATPase
PubMed: 30488358
DOI: 10.1007/s10158-018-0221-7 -
Biomedical Journal Oct 2022The brain is the most unexplored part of our body. The lack of sufficient tools has hindered our understanding of the brain and the associated diseases. The study of... (Review)
Review
The brain is the most unexplored part of our body. The lack of sufficient tools has hindered our understanding of the brain and the associated diseases. The study of neurons and the neuronal network will help elucidate how the brain functions and related disorders. Over the last few decades, an increasing number of techniques have been reported to study neurons and neuronal communication in vitro, ex vivo, and in vivo. These methods have pushed the boundaries of neuroscience and elucidated more information than ever before; however, much more requires to be done to understand the brain in its entirety. In this review article, I discuss the principles and the advantages and disadvantages of the classical electrode-based recording techniques and the optical imaging-based methods, which have aided neuroscientists in understanding neuronal communication.
Topics: Humans; Membrane Potentials; Neurons; Brain; Fluorescent Dyes
PubMed: 35667642
DOI: 10.1016/j.bj.2022.05.007 -
Archives of Insect Biochemistry and... Jun 2022The functioning of voltage-dependent K channels (Kv) may correlate with the physiological state of brain in organisms, including the sleep in Drosophila. Apparently, all... (Review)
Review
The functioning of voltage-dependent K channels (Kv) may correlate with the physiological state of brain in organisms, including the sleep in Drosophila. Apparently, all major types of K currents are expressed in CNS of this model organism. These are the Shab-Kv2, Shaker-Kv1, Shal-Kv4, and Shaw-Kv3 α subunits and can be deciphered by patch-clamp technique. Although it is plausible that some of these channels may play a prevailing role in sleep or wakefulness, several of recent data are not conclusive. It needs to be defined that indeed the frequency of action potentials in large ventral lateral pacemaker neurons is either higher or lower during the morning or night because of an increased Kv3 and Kv4 currents, respectively. The outcomes of dynamic-clamp approach in combination with electrophysiology in insects are unreliable in contrast to those in mammalian neurons. Since the addition of virtual Kv conductance during any Zeitgeber time should not significantly alter the resting membrane potential. This review explains the Drosophila sleep behavior based on neural activity with respect to K current-driven action potential rate.
Topics: Animals; Drosophila; Mammals; Membrane Potentials; Neurons; Patch-Clamp Techniques; Sleep
PubMed: 35313039
DOI: 10.1002/arch.21884 -
International Journal of Molecular... Apr 2023During the last seventy years, studies on mammalian sperm cells have demonstrated the essential role of capacitation, hyperactivation and the acrosome reaction in the... (Review)
Review
During the last seventy years, studies on mammalian sperm cells have demonstrated the essential role of capacitation, hyperactivation and the acrosome reaction in the acquisition of fertilization ability. These studies revealed the important biochemical and physiological changes that sperm undergo in their travel throughout the female genital tract, including changes in membrane fluidity, the activation of soluble adenylate cyclase, increases in intracellular pH and Ca and the development of motility. Sperm are highly polarized cells, with a resting membrane potential of about -40 mV, which must rapidly adapt to the ionic changes occurring through the sperm membrane. This review summarizes the current knowledge about the relationship between variations in the sperm potential membrane, including depolarization and hyperpolarization, and their correlation with changes in sperm motility and capacitation to further lead to the acrosome reaction, a calcium-dependent exocytosis process. We also review the functionality of different ion channels that are present in spermatozoa in order to understand their association with human infertility.
Topics: Animals; Male; Humans; Female; Membrane Potentials; Sperm Capacitation; Semen; Sperm Motility; Spermatozoa; Ion Channels; Calcium; Mammals
PubMed: 37108159
DOI: 10.3390/ijms24086995