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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 -
Toxicology Dec 2021Mefloquine is a quinoline-based compound widely used as an antimalarial drug, particularly in chemoprophylaxis. Although decades of research have identified various... (Review)
Review
Mefloquine is a quinoline-based compound widely used as an antimalarial drug, particularly in chemoprophylaxis. Although decades of research have identified various aspects of mefloquine's anti-Plasmodium properties, toxic effects offset its robust use in humans. Mefloquine exerts harmful effects in several types of human cells by targeting many of the cellular lipids, proteins, and complexes, thereby blocking a number of downstream signaling cascades. In general, mefloquine modulates several cellular phenomena, such as alteration of membrane potential, induction of oxidative stress, imbalance of ion homeostasis, disruption of metabolism, failure of organelle function, etc., leading to cell cycle arrest and programmed cell death. This review aims to summarize the information on functional and mechanistic findings related to the cytotoxic effects of mefloquine.
Topics: Animals; Antimalarials; Apoptosis; Cell Cycle Checkpoints; Humans; Mefloquine; Membrane Potentials; Oxidative Stress
PubMed: 34678321
DOI: 10.1016/j.tox.2021.152995 -
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 -
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 -
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 -
Neurochemical Research Jan 2020Astrocytes support glutamatergic neurotransmission in the central nervous system through multiple mechanisms which include: (i) glutamate clearance and control over... (Review)
Review
Astrocytes support glutamatergic neurotransmission in the central nervous system through multiple mechanisms which include: (i) glutamate clearance and control over glutamate spillover due to operation of glutamate transporters; (ii) supply of obligatory glutamate precursor glutamine via operation of glutamate-glutamine shuttle; (iii) supply of L-serine, the indispensable precursor of positive NMDA receptors neuromodulator D-serine and (iv) through overall homoeostatic control of the synaptic cleft. Astroglial cells express an extended complement of ionotropic and metabotropic glutamate receptors, which mediate glutamatergic input to astrocytes. In particular a sub-population of astrocytes in the cortex and in the spinal cord express specific type of NMDA receptors assembled from two GluN1, one GluN2C or D and one GluN3 subunits. This composition underlies low Mg sensitivity thus making astroglial NMDA receptors operational at resting membrane potential. These NMDA receptors generate ionic signals in astrocytes and are linked to several astroglial homoeostatic molecular cascades.
Topics: Animals; Astrocytes; Cerebral Cortex; Humans; Membrane Potentials; Nerve Net; Receptors, N-Methyl-D-Aspartate
PubMed: 30767094
DOI: 10.1007/s11064-019-02750-3 -
Advances in Experimental Medicine and... 2021Optogenetic approaches combine the power to allocate optogenetic tools (proteins) to specific cell populations (defined genetically or functionally) and the use of... (Review)
Review
Optogenetic approaches combine the power to allocate optogenetic tools (proteins) to specific cell populations (defined genetically or functionally) and the use of light-based interfaces between biological wetware (cells and tissues) and hardware (controllers and recorders). The optogenetic toolbox contains two main compartments: tools to interfere with cellular processes and tools to monitor cellular events. Among the latter are genetically encoded voltage indicators (GEVIs). This chapter outlines the development, current state of the art and prospects of emerging optical GEVI imaging technologies.
Topics: Cells; Luminescent Proteins; Membrane Potentials; Optogenetics
PubMed: 33398815
DOI: 10.1007/978-981-15-8763-4_12 -
Trends in Microbiology Apr 2020All cellular membranes have the functionality of generating and maintaining the gradients of electrical and electrochemical potentials. Such potentials were generally... (Review)
Review
All cellular membranes have the functionality of generating and maintaining the gradients of electrical and electrochemical potentials. Such potentials were generally thought to be an essential but homeostatic contributor to complex bacterial behaviors. Recent studies have revised this view, and we now know that bacterial membrane potential is dynamic and plays signaling roles in cell-cell interaction, adaptation to antibiotics, and sensation of cellular conditions and environments. These discoveries argue that bacterial membrane potential dynamics deserve more attention. Here, we review the recent studies revealing the signaling roles of bacterial membrane potential dynamics. We also introduce basic biophysical theories of the membrane potential to the microbiology community and discuss the needs to revise these theories for applications in bacterial electrophysiology.
Topics: Anti-Bacterial Agents; Bacteria; Biofilms; Biophysics; Drug Resistance, Bacterial; Electrophysiology; Eukaryota; Membrane Potentials
PubMed: 31952908
DOI: 10.1016/j.tim.2019.12.008