Membrane Ion Channels and Ion Currents

The Neuron ◽  
2015 ◽  
pp. 63-84
Author(s):  
Irwin B. Levitan ◽  
Leonard K. Kaczmarek

Electrical activity in neurons (and other kinds of cells) results from the movement of ions across the plasma membrane through specialized membrane proteins known as ion channels. Exquisitely sensitive patch clamp techniques are available to measure the current passing through single ion channels, as well as the macroscopic membrane current carried by a population of ion channels. These techniques have enabled the detailed characterization of various essential properties of ion channels, including their selectivity for particular ions, their pharmacology, and the way their activity is regulated by membrane voltage and other factors. There are many different kinds of ion channels in the neuronal plasma membrane, and their activities sum to generate action potentials and complex patterns of action potential firing.

The Neuron ◽  
2015 ◽  
pp. 103-126
Author(s):  
Irwin B. Levitan ◽  
Leonard K. Kaczmarek

The flow of ions down their electrochemical gradients, through populations of ion channels in the neuronal plasma membrane, gives rise to transmembrane ion currents. It is the sum of the various currents flowing at any point in time that determines the neuron’s membrane potential. Thus the normal firing pattern of a neuron, and its response to different kinds of stimulation, can be seen as a play of interactions among the currents flowing through the different kinds of ion channels in its membrane. The activities of the sodium and potassium channels responsible for axonal action potentials are themselves dependent on voltage. Voltage clamp studies, which allow the measurement of the current flowing through these channels at fixed voltage, have provided a detailed understanding of the sequence of changes in sodium and potassium channel activity that give rise to action potentials.


2005 ◽  
Vol 89 (6) ◽  
pp. 3741-3756 ◽  
Author(s):  
J.M.A.M. Kusters ◽  
M.M. Dernison ◽  
W.P.M. van Meerwijk ◽  
D.L. Ypey ◽  
A.P.R. Theuvenet ◽  
...  

2011 ◽  
Vol 16 (8) ◽  
pp. 910-916 ◽  
Author(s):  
Sonja Stoelzle ◽  
Alison Haythornthwaite ◽  
Ralf Kettenhofen ◽  
Eugen Kolossov ◽  
Heribert Bohlen ◽  
...  

Cardiovascular side effects are critical in drug development and have frequently led to late-stage project terminations or even drug withdrawal from the market. Physiologically relevant and predictive assays for cardiotoxicity are hence strongly demanded by the pharmaceutical industry. To identify a potential impact of test compounds on ventricular repolarization, typically a variety of ion channels in diverse heterologously expressing cells have to be investigated. Similar to primary cells, in vitro–generated stem cell–derived cardiomyocytes simultaneously express cardiac ion channels. Thus, they more accurately represent the native situation compared with cell lines overexpressing only a single type of ion channel. The aim of this study was to determine if stem cell–derived cardiomyocytes are suited for use in an automated patch clamp system. The authors show recordings of cardiac ion currents as well as action potential recordings in readily available stem cell–derived cardiomyocytes. Besides monitoring inhibitory effects of reference compounds on typical cardiac ion currents, the authors revealed for the first time drug-induced modulation of cardiac action potentials in an automated patch clamp system. The combination of an in vitro cardiac cell model with higher throughput patch clamp screening technology allows for a cost-effective cardiotoxicity prediction in a physiologically relevant cell system.


The plant growth regulator abscisic acid triggers closing of stomata in the leaf epidermis in response to water stress. Recent tracer flux studies, patch-clamp studies, fluorometric Ca 2+ measurements and microelectrode experiments have provided insight into primary transduction mechanisms by which abscisic acid causes stomatal closing. Data show that abscisic acid activates non-selective Ca 2+ permeable ion channels in the plasma membrane of guard cells. The resulting elevation in the free Ca 2+ concentration in the cytosol of guard cells, and the resulting membrane depolarization as well as other unidentified Ca 2+ independent mechanisms are suggested to contribute to activation of voltage- and second messenger-dependent anion channels and outward rectifying K + channels. Recent data suggest the involvement of two types of anion channels in the regulation of stomatal movements, which provide highly distinct mechanisms for anion efflux and depolarization. A novely characterized ‘S-type’ anion channel is likely to provide a key mechanism for long-term depolarization and sustained anion efflux during closing of stomata. Patch-clamp studies have revealed the presence of a network of K + , anion and non-selective Ca 2+ -permeable channels in the plasma membrane of a higher plant cell. The integrated control of these guard cell ion channels by abscisic acid can provide control over K + and anion efflux required for stomatal closing.


2019 ◽  
Author(s):  
Mattia L. DiFrancesco ◽  
Francesco Lodola ◽  
Elisabetta Colombo ◽  
Luca Maragliano ◽  
Giuseppe M. Paternò ◽  
...  

ABSTRACTOptical technologies allowing modulation of neuronal activity at high spatio-temporal resolution are becoming paramount in neuroscience. We engineered novel light-sensitive molecules by adding polar groups to a hydrophobic backbone containing azobenzene and azepane moieties. We demonstrate that the probes stably partition into the plasma membrane, with affinity for lipid rafts, and cause thinning of the bilayer through their trans-dimerization in the dark. In neurons pulse-labeled with the compound, light induces a transient hyperpolarization followed by a delayed depolarization that triggers action potential firing. The fast hyperpolarization is attributable to a light-dependent decrease in capacitance due to membrane relaxation that follows disruption of the azobenzene dimers. The physiological effects are persistent and can be evoked in vivo after labeling the mouse somatosensory cortex. These data demonstrate the possibility to trigger neural activity in vitro and in vivo by modulating membrane capacitance, without directly affecting ion channels or local temperature.


The Neuron ◽  
2015 ◽  
pp. 41-62
Author(s):  
Irwin B. Levitan ◽  
Leonard K. Kaczmarek

In neurons, information is carried from one part of the cell to another in the form of action potentials—large and rapidly reversible fluctuations in electrical voltage across the plasma membrane that propagate along the axon. Different neurons exhibit different patterns of action potential firing. Some neurons are normally silent; their membrane potential remains at the resting potential unless the firing of action potentials is triggered by some external stimulus, and they return to their non-firing state when the stimulus is no longer present. Many neurons exhibit more complex endogenous electrical activity, often firing action potentials in a regular pattern without an external stimulus. The electrical properties of a neuron are subject to modulation by input from the environment, including sensory information from the outside world, hormones released from other parts of the organism, and chemical and electrical signals from other neurons to which the neuron is functionally connected.


2012 ◽  
Vol 92 (4) ◽  
pp. 1777-1811 ◽  
Author(s):  
Rainer Hedrich

Since the first recordings of single potassium channel activities in the plasma membrane of guard cells more than 25 years ago, patch-clamp studies discovered a variety of ion channels in all cell types and plant species under inspection. Their properties differed in a cell type- and cell membrane-dependent manner. Guard cells, for which the existence of plant potassium channels was initially documented, advanced to a versatile model system for studying plant ion channel structure, function, and physiology. Interestingly, one of the first identified potassium-channel genes encoding the Shaker-type channel KAT1 was shown to be highly expressed in guard cells. KAT1-type channels from Arabidopsis thaliana and its homologs from other species were found to encode the K+-selective inward rectifiers that had already been recorded in early patch-clamp studies with guard cells. Within the genome era, additional Arabidopsis Shaker-type channels appeared. All nine members of the Arabidopsis Shaker family are localized at the plasma membrane, where they either operate as inward rectifiers, outward rectifiers, weak voltage-dependent channels, or electrically silent, but modulatory subunits. The vacuole membrane, in contrast, harbors a set of two-pore K+ channels. Just very recently, two plant anion channel families of the SLAC/SLAH and ALMT/QUAC type were identified. SLAC1/SLAH3 and QUAC1 are expressed in guard cells and mediate Slow- and Rapid-type anion currents, respectively, that are involved in volume and turgor regulation. Anion channels in guard cells and other plant cells are key targets within often complex signaling networks. Here, the present knowledge is reviewed for the plant ion channel biology. Special emphasis is drawn to the molecular mechanisms of channel regulation, in the context of model systems and in the light of evolution.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Marie-France Martin-Eauclaire ◽  
Pierre E. Bougis

K+channels selectively transport K+ions across cell membranes and play a key role in regulating the physiology of excitable and nonexcitable cells. Their activation allows the cell to repolarize after action potential firing and reduces excitability, whereas channel inhibition increases excitability. In eukaryotes, the pharmacology and pore topology of several structural classes of K+channels have been well characterized in the past two decades. This information has come about through the extensive use of scorpion toxins. We have participated in the isolation and in the characterization of several structurally distinct families of scorpion toxin peptides exhibiting different K+channel blocking functions. In particular, the venom from the Moroccan scorpionAndroctonus mauretanicus mauretanicusprovided several high-affinity blockers selective for diverse K+channels  (SKCa,  Kv4.x, and  Kv1.x K+channel families). In this paper, we summarize our work on these toxin/channel interactions.


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