The Cell Membrane in the Steady State
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
The electrical properties of the cell are essentially those of the cell membrane. The chapter begins therefore with a description of the basic structure of the cell membrane, highlighting its electrical properties. As ion channels play a vital role in the electrical behavior of the cell by controlling which ions cross the membrane and under what conditions, ion channels are discussed in general terms. The distribution of some major ions across the cell membrane is then considered, leading to the inference that there must be an ion pump that actively extrudes Na+. It is shown how the pump plays a vital role in establishing osmotic equilibrium and an electrochemical potential difference across the cell membrane. This electrochemical potential difference is associated with a resting membrane voltage and allows the generation of electric signals by the cell. The origin of the resting membrane voltage is explained, quantified, and interpreted in terms of a useful and commonly invoked equivalent circuit that includes conductances and equilibrium voltages of the various ions. Two interesting electrical properties of the membrane are discussed, namely, rectification and reactance. It is shown that, basically, rectification arises from unequal distribution of ions on the two sides of the membrane, whereas reactance, which could be inductive or capacitive, is manifested by conductances that are nonlinear and time-varying. The chapter ends with a direct analogy between ionic and semiconductor systems.
Basic Thermal Physiology: What Processes Lead to the Temperature Distribution on the Skin Surface
Kurt Ammer, Francis Ring in The Thermal Human Body, 2019
Another important function of a living organism is processing and distribution of information. Sensing and transport of information either arriving at the body surface or generated inside of body structures, is the task of the peripheral sensory and autonomic nerve system. The processing of this information takes place in the spinal cord, and the brain. While electrical current achieves the speed of information in nerves, this current is generated due to the exchange of ions across the cell membrane of nerve fibres. These electrical phenomena are coupled to the release of a chemical messenger (neurotransmitter) from the nerve cell. Once released, this chemical messenger can diffuse across the gap to the target cell, where it can bind and interact with a specific protein (receptor) embedded in the cell membrane. This process of binding leads to a series or cascade of secondary effects which result either in a flow of ions across the cell membrane, or in the switching on (or off) of enzymes inside the target cell. A biological response then results, such as the contraction of a muscle cell or the activation of fatty acid metabolism in a fat cell [1]. The structure of ion channels is in focus of intensive research. These pores in the cell membrane are generated by proteins, which are expressed under the influence of chemical, electrical or temperature stimuli.
Bert Sakmann (b. 1942) and Erwin Neher (b. 1944)
Andrew P. Wickens in Key Thinkers in Neuroscience, 2018
The study of ion channels is one of the major endeavours of modern cell biology because they are crucial components in the activity of living cells. Ion channels are found in the membrane of most cells and they allow positively or negatively charged ions to pass in and out. A theory attempting to explain how the movement of ions produced the nerve impulse had first been proposed by the German Julius Bernstein in 1902. But it was the work of Hodgkin and Huxley that ignited the field in 1952, when they provided a mathematical description of how sodium (Na+) and potassium (K+) ions flowed through the nerve axon membrane. Despite this, the existence of ion channels was far from proven, not least because they are far too tiny to be seen under the most powerful microscope. There was also much speculation concerning the mechanism by which the ion channel opened. Most researchers believed the ion channel was some type of specialised “pore” that only allowed the appropriate ion through at precisely the right moment. But how it managed this feat was unclear. Yet, there were other possibilities including one where the ions were carried through the membrane on some type of transporter system. In fact, this was the option that Hodgkin and Huxley had considered most likely. Unfortunately, for neurophysiologists at the time, there seemed no way the ion channel question could ever be answered or resolved.
Automated patch clamp in drug discovery: major breakthroughs and innovation in the last decade
Published in Expert Opinion on Drug Discovery, 2021
Alison Obergrussberger, Søren Friis, Andrea Brüggemann, Niels Fertig
Patch-clamp electrophysiology remains an important technique in studying ion channels; indeed, it is still considered the gold standard since it was first described by Neher and Sakmann in the 1970s [1]. Ion channels are integral membrane proteins which allow ion current flow across the cell membrane. They are involved in almost all physiological processes, and their malfunction underlies many disease states, making them important pharmacological targets. Conventional patch clamp is a very information-rich technique, but it requires skilled personnel to perform experiments, and typically, only one experiment can be performed at a time. In the late 1990s and early 2000s, the field of ion-channel research was revolutionized by the development of the automated patch-clamp (APC) technique. The most successful approach involved replacing the patch-clamp pipette with a planar substrate (for review, see [2]), making the experiments easier to perform and offering the option for recording multiple cells in parallel. In the last two decades, much has changed in the field of ion-channel drug discovery and APC, with increased throughput and enhanced simplicity. We summarize the main changes in the last decade and attempt to look into the future of what’s to come.
Using Xenopus oocytes in neurological disease drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Steven L. Zeng, Leland C. Sudlow, Mikhail Y. Berezin
Ion channels act as entryways for ions to penetrate the otherwise impermeable cell membrane. Along with supporting regulatory and other proteins, ion channels establish a connection between the environment and the neurons. The opening and closing of these channels are highly regulated. Ion channels respond only to specific signals, such as binding of a neurotransmitter, alteration in electrical membrane potential, phosphorylation of one or more subunits, and so on. Malfunctioning ion channels are the major common causes of a large number of neurological disorders [6,7]. Aberrant K+ and other ion channels are responsible for neuromyotonia [8], episodic ataxia type-1 [9] and benign familial neonatal convulsions [10] among many other genetic and acquired neurological disorders [11]. Defects in voltage-gated Na+ channels lead to pain [12] and epilepsy [13]. Calcium channels are accountable for several psychiatric disorders [14]. Advancement in the study of ion channels has made it possible to evaluate channel dysfunctions at the various levels from the single channel to the complex neuronal systems, and the whole organism.
Effect of Imipramine on radiosensitivity of Prostate Cancer: An In Vitro Study
Published in Cancer Investigation, 2019
Songul Barlaz Us, Fatma Sogut, Metin Yildirim, Derya Yetkin, Serap Yalin, Sakir Necat Yilmaz, Ulku Comelekoglu
Ion channels are multimeric membrane proteins allowing the passage of ions. These proteins play important role in neural transmission, hormone secretion, muscle contraction and cell proliferation. They are opened or closed by specific stimuli such as membrane voltage, stretch, pressure, ligand-binding and temperature (37). It has been reported that voltage-gated potassium channels have been associated with many diseases including cancer (38). Among these channels, EAG1 has a special importance in the etiology of cancer due to its limited distribution in normal tissues and its role in tumor cell proliferation (37). EAG1 has been reported to be expressed in lung, breast, cervical, prostate, colon, ovarian and gastric cancers; gliomas; leukemia and different types of sarcoma (34,39,40). In the present study, EAG1 channel activity was determined by whole cell patch clamp technique. We measured current amplitudes in control, IMI, RAD and IMI + RAD groups. We observed that, amplitude in the IMI, RAD and IMI + RAD were groups reduced by 61.0%, 8.6% and 15.1% with compared to control, respectively. Inhibition of EAG1 channel current is associated with a decrease in proliferation of tumor cells (37). In the RAD and IMI + RAD groups, we did not observe significant inhibiton of EAG1 channel currents. In the RAD and IMI + RAD groups, currents of EAG1 were significantly lower than IMI group. To the best of our knowledge, this is the first study which investigation the effect of radiation therapy on EAG1 channel currents.