Ion Channels
Stephen H. White, Gunnar von Heijne, Donald M. Engelman in Cell Boundaries, 2021
How do cells recognize and respond to their environments? Single cells are able to seek food by chemotaxis, respond to threats such as osmotic stress, and outgrow the competition by being efficient with available resources, to note only a few of the many responses. Cells in multicellular organisms, on the other hand, must work in concert over long distances with other cells and tissues to respond to environmental challenges in a coordinated manner. The nervous systems of higher organisms allow high-speed communication between diverse cells and tissues by means of electrical and chemical signaling. It is exciting that we are beginning to understand in chemical detail these processes in living cells. Without fast signaling, we would not be able to move or think as we do. Ion channels dominate fast signaling. They do this through exquisite control of ion flows across membrane barriers. The lipid bilayer of cell membranes is an excellent barrier; neither ions nor water can cross this thin hydrocarbon barrier with ease (Chapters 1 and 2). As a result, it is possible for proteins embedded in the bilayer to regulate the passive flow of ions, water, and other molecules across the membrane.
Endogenous Activation and Neurophysiological Functions of Acid-Sensing Ion Channels
Long-Jun Wu in Nonclassical Ion Channels in the Nervous System, 2021
Protons are considered to constitute important signals for cell communications under both physiological and pathological conditions. Recently, emerging evidence has been provided to support protons as neurotransmitters that are involved in synaptic transmission and plasticity. Deficient or exaggerated proton signaling is also one essential contributing factor for those neurological diseases associated with severe tissue acidosis. Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na + channel superfamily, are one of the most critical sensors of extracellular pH changes. These channels consist of six subunits encoded by four genes. In this chapter, we summarize previous studies concerning the potential endogenous proton sources for activating ASICs, including metabolic production of protons and acidification niche and other proton generators. We next discuss the various functions of ASICs in synapse development and plasticity, as well as the region-specific roles of ASICs in amygdala, retina, and dorsal root ganglia. Finally, we presented some unresolved issues and future research directions.
Physiology of Excitable Cells
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
This chapter examines the physiology of some excitable cells. It examines the ionic basis for the resting membrane potential, followed by the formation of the action potential for both nerves and muscle. The chapter describes voltage-sensitive membrane ion channels and discusses their role in the action potential. Chemical communication between excitable cells is examined by investigating the interaction of receptors, ion channels, G proteins and intracellular messengers. Afferent nerves are activated by special sense organs and transmit this information by electrical axonal activation and release of neurotransmitters, altering the membrane potential and function of central nervous system cells. Low-intensity electrical stimuli applied to nerves produce electrotonic, or local, potentials, which fall exponentially from the site of stimulus in accordance with the proposed electrical circuit model of the membrane. The basis of the action potential is that depolarization opens sodium, potassium or calcium channels that are gated by the membrane voltage.
Advances in functional assays for high-throughput screening of ion channels targets
Published in Expert Opinion on Drug Discovery, 2010
Shephali Trivedi, Jay Liu, Ruifeng Liu, Robert Bostwick
Importance of the field: Ion channels are important targets for many disease areas but are challenging to screen due to lack of technologies enabling robust high-throughput assays, particularly for state-dependent interactions. Areas covered in this review: Current assay technologies used to measure ion channel function are reviewed and assessed for use in high-throughput screening (HTS). An iterative approach to screening is evaluated as an alternative to full collection screening in order to take advantage of low-throughput, high cost assays that yield high quality data. What the reader will gain: The reader will gain an understanding of the advantages and disadvantages of various assay techniques used to screen ion channels and their suitability for use in HTS. Take home message: Assays that directly measure ion channel function are prone to less artifact and higher hit confirmation in screening than those using an indirect measure but they are usually lower throughput. However, an iterative approach to screening can make the relatively lower throughput techniques amenable for use in interrogating large collections of compounds.
Modification of cardiovascular ion channels by gene therapy
Published in Expert Review of Cardiovascular Therapy, 2009
Sabine Telemaque, James D Marsh
Delivery of genes to the heart and vasculature for therapeutic purposes is an exciting strategy that is approaching clinical reality. Abnormalities of expression or function of ion channels is central to many cardiovascular diseases and gene delivery to modify ion channels is an appealing alternative to traditional therapy with small-molecule drugs. Potential therapeutic targets include hypertrophy and heart failure, atrioventricular node modification in atrial fibrillation, ventricular tachycardia and hypertension. Numerous approaches for gene delivery are under development, including use of tissue-specific promoters in viral vectors. For other applications, such as development of biological pacemakers, cells can be transduced with pacemaker genes in vitro, and then the cells implanted within the heart. There are short-term hurdles to therapeutic gene delivery to modify cardiovascular ion channels, but in the intermediate and longer term, the outlook is promising.
Ion channels as therapeutic antibody targets
Published in mAbs, 2019
Catherine J. Hutchings, Paul Colussi, Theodore G. Clark
It is now well established that antibodies have numerous potential benefits when developed as therapeutics. Here, we evaluate the technical challenges of raising antibodies to membrane-spanning proteins together with enabling technologies that may facilitate the discovery of antibody therapeutics to ion channels. Additionally, we discuss the potential targeting opportunities in the anti-ion channel antibody landscape, along with a number of case studies where functional antibodies that target ion channels have been reported. Antibodies currently in development and progressing towards the clinic are highlighted.
Related Knowledge Centers
- Membrane Transport Proteins
- Resting Potential
- Sodium
- Ligands
- Trpm
- Intracellular Signaling Peptides & Proteins
- Mitochondrial Membranes