ElectrophysiologyElectrophysiology (from Greek ἥλεκτ, ēlektron, "amber" [see the etymology of "electron"]; φύσις, physis, "nature, origin"; and -λογία, -logia) is the branch of physiology that studies the electrical properties of biological cells and tissues. It involves measurements of voltage changes or electric current or manipulations on a wide variety of scales from single ion channel proteins to whole organs like the heart. In neuroscience, it includes measurements of the electrical activity of neurons, and, in particular, action potential activity.
Patch clampThe patch clamp technique is a laboratory technique in electrophysiology used to study ionic currents in individual isolated living cells, tissue sections, or patches of cell membrane. The technique is especially useful in the study of excitable cells such as neurons, cardiomyocytes, muscle fibers, and pancreatic beta cells, and can also be applied to the study of bacterial ion channels in specially prepared giant spheroplasts. Patch clamping can be performed using the voltage clamp technique.
Voltage clampThe voltage clamp is an experimental method used by electrophysiologists to measure the ion currents through the membranes of excitable cells, such as neurons, while holding the membrane voltage at a set level. A basic voltage clamp will iteratively measure the membrane potential, and then change the membrane potential (voltage) to a desired value by adding the necessary current. This "clamps" the cell membrane at a desired constant voltage, allowing the voltage clamp to record what currents are delivered.
Ion channelIon channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.
Action potentialAn action potential occurs when the membrane potential of a specific cell rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and in some plant cells. Certain endocrine cells such as pancreatic beta cells, and certain cells of the anterior pituitary gland are also excitable cells.
Membrane potentialMembrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges to move from the internal to exterior cellular environments and vice versa, as long as there is no acquisition of kinetic energy or the production of radiation. The concentration gradients of the charges directly determine this energy requirement.
Threshold potentialIn electrophysiology, the threshold potential is the critical level to which a membrane potential must be depolarized to initiate an action potential. In neuroscience, threshold potentials are necessary to regulate and propagate signaling in both the central nervous system (CNS) and the peripheral nervous system (PNS). Most often, the threshold potential is a membrane potential value between –50 and –55 mV, but can vary based upon several factors.
Ligand-gated ion channelLigand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter. When a presynaptic neuron is excited, it releases a neurotransmitter from vesicles into the synaptic cleft. The neurotransmitter then binds to receptors located on the postsynaptic neuron.
Sodium channelSodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels. They are classified into 2 types: In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. These channels go through three different states called resting, active and inactive states.
Microelectrode arrayMicroelectrode arrays (MEAs) (also referred to as multielectrode arrays) are devices that contain multiple (tens to thousands) microelectrodes through which neural signals are obtained or delivered, essentially serving as neural interfaces that connect neurons to electronic circuitry. There are two general classes of MEAs: implantable MEAs, used in vivo, and non-implantable MEAs, used in vitro. Neurons and muscle cells create ion currents through their membranes when excited, causing a change in voltage between the inside and the outside of the cell.
Postsynaptic potentialPostsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse. Postsynaptic potentials are graded potentials, and should not be confused with action potentials although their function is to initiate or inhibit action potentials. They are caused by the presynaptic neuron releasing neurotransmitters from the terminal bouton at the end of an axon into the synaptic cleft. The neurotransmitters bind to receptors on the postsynaptic terminal, which may be a neuron or a muscle cell in the case of a neuromuscular junction.
Cardiac electrophysiologyCardiac electrophysiology is a branch of cardiology and basic science focusing on the electrical activities of the heart. The term is usually used in clinical context, to describe studies of such phenomena by invasive (intracardiac) catheter recording of spontaneous activity as well as of cardiac responses to programmed electrical stimulation - clinical cardiac electrophysiology. However, cardiac electrophysiology also encompasses basic research and translational research components.
High-throughput screeningHigh-throughput screening (HTS) is a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology, materials science and chemistry. Using robotics, data processing/control software, liquid handling devices, and sensitive detectors, high-throughput screening allows a researcher to quickly conduct millions of chemical, genetic, or pharmacological tests. Through this process one can quickly recognize active compounds, antibodies, or genes that modulate a particular biomolecular pathway.
Voltage-gated ion channelVoltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels. They have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change.
Virtual screeningVirtual screening (VS) is a computational technique used in drug discovery to search libraries of small molecules in order to identify those structures which are most likely to bind to a drug target, typically a protein receptor or enzyme. Virtual screening has been defined as "automatically evaluating very large libraries of compounds" using computer programs. As this definition suggests, VS has largely been a numbers game focusing on how the enormous chemical space of over 1060 conceivable compounds can be filtered to a manageable number that can be synthesized, purchased, and tested.
Patch-sequencingPatch-sequencing (patch-seq) is a method designed for tackling specific problems involved in characterizing neurons. As neural tissues are one of the most transcriptomically diverse populations of cells, classifying neurons into cell types in order to understand the circuits they form is a major challenge for neuroscientists. Combining classical classification methods with single cell RNA-sequencing post-hoc has proved to be difficult and slow.
High-content screeningHigh-content screening (HCS), also known as high-content analysis (HCA) or cellomics, is a method that is used in biological research and drug discovery to identify substances such as small molecules, peptides, or RNAi that alter the phenotype of a cell in a desired manner. Hence high content screening is a type of phenotypic screen conducted in cells involving the analysis of whole cells or components of cells with simultaneous readout of several parameters.
Drug designDrug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it.
Clinical cardiac electrophysiologyClinical cardiac electrophysiology (also referred to as cardiac electrophysiology, arrhythmia services, or electrophysiology), is a branch of the medical specialty of cardiology and is concerned with the study and treatment of rhythm disorders of the heart. Cardiologists with expertise in this area are usually referred to as electrophysiologists. Electrophysiologists are trained in the mechanism, function, and performance of the electrical activities of the heart.
Inhibitory postsynaptic potentialAn inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential. IPSPs were first investigated in motorneurons by David P. C. Lloyd, John Eccles and Rodolfo Llinás in the 1950s and 1960s. The opposite of an inhibitory postsynaptic potential is an excitatory postsynaptic potential (EPSP), which is a synaptic potential that makes a postsynaptic neuron more likely to generate an action potential.
