Clay Armstrong

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Clay Margrave Armstrong (born 1934) [1] is an American physiologist and a former student of Andrew Fielding Huxley. Armstrong received his MD from Washington University School of Medicine in 1960. He is currently emeritus professor of Physiology at the University of Pennsylvania. [2] He has also held professorial appointments at Duke University and the University of Rochester.

Armstrong was awarded the Louisa Gross Horwitz Prize from Columbia University in 1996, and the Albert Lasker Award for Basic Medical Research (shared with Bertil Hille and Roderick MacKinnon) in 1999, [3] for his seminal contributions to our understanding of the functions of ion channel proteins in nerve cells. Armstrong was elected to the National Academy of Sciences in 1987, and was elected as a Fellow of the American Academy of Arts and Sciences in 1999. [1] He won the 2001 Gairdner Foundation International Award. [4]

Armstrong is married to noted scientist Clara Franzini-Armstrong. [5]

Ideas and influence

Much of the current understanding of ion channel structure and function can be attributed to the notion proposed by Clay Armstrong (with Bertil Hille). Armstrong provided the first general description of the K+ ion channel pore, including the fundamental ideas of a selectivity filter that can allow the rapid flow of K+ while excluding the flow of Na+ across the cell membrane; a wide inner vestibule; and a molecular gating element at the cytoplasmic side of the channel that controls the flow of ions through the pore. [6] In addition, Armstrong's studies (with Francisco Bezanilla) that described the first measurement of charge movement associated with the activation of Na+-selective ion channels laid the groundwork for the current understanding of the molecular basis of electrical signaling in nerve and muscle cells. [7]

A consistent feature of Armstrong's contributions is the quantitative nature of his work, combined with clear and concise descriptions of the underlying mechanism.[ citation needed ]

Related Research Articles

Ion channel Pore-forming membrane protein

Ion 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 potential Neuron communication by electric impulses

In physiology, an action potential (AP) occurs when the membrane potential of a specific cell location 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, endocrine cells and in some plant cells.

Potassium channel Ion channel that selectively passes K+

Potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions.

Voltage-gated ion channel Type of ion channel transmembrane protein

Voltage-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. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals. Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl−) ions have been identified. The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, between the sides of the cell membrane.

Cyclic nucleotide–gated ion channel

Cyclic nucleotide–gated ion channels or CNG channels are ion channels that function in response to the binding of cyclic nucleotides. CNG channels are nonselective cation channels that are found in the membranes of various tissue and cell types, and are significant in sensory transduction as well as cellular development. Their function can be the result of a combination of the binding of cyclic nucleotides and either a depolarization or a hyperpolarization event. Initially discovered in the cells that make up the retina of the eye, CNG channels have been found in many different cell types across both the animal and the plant kingdoms. CNG channels have a very complex structure with various subunits and domains that play a critical role in their function. CNG channels are significant in the function of various sensory pathways including vision and olfaction, as well as in other key cellular functions such as hormone release and chemotaxis. CNG channels have also been found to exist in prokaryotes, including many spirochaeta, though their precise role in bacterial physiology remains unknown.

Inward-rectifier potassium channel Group of transmembrane proteins that passively transport potassium ions

Inward-rectifier potassium channels (Kir, IRK) are a specific lipid-gated subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are activated by phosphatidylinositol 4,5-bisphosphate (PIP2). The malfunction of the channels has been implicated in several diseases. IRK channels possess a pore domain, homologous to that of voltage-gated ion channels, and flanking transmembrane segments (TMSs). They may exist in the membrane as homo- or heterooligomers and each monomer possesses between 2 and 4 TMSs. In terms of function, these proteins transport potassium (K+), with a greater tendency for K+ uptake than K+ export. The process of inward-rectification was discovered by Denis Noble in cardiac muscle cells in 1960s and by Richard Adrian and Alan Hodgkin in 1970 in skeletal muscle cells.

Sodium 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 and can be classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change ("voltage-gated", "voltage-sensitive", or "voltage-dependent" sodium channel; also called "VGSCs" or "Nav channel") or a binding of a substance (a ligand) to the channel (ligand-gated sodium channels).

Hodgkin–Huxley model Describes how neurons transmit electric signals

The Hodgkin–Huxley model, or conductance-based model, is a mathematical model that describes how action potentials in neurons are initiated and propagated. It is a set of nonlinear differential equations that approximates the electrical characteristics of excitable cells such as neurons and muscle cells. It is a continuous-time dynamical system.

The shaker (Sh) gene, when mutated, causes a variety of atypical behaviors in the fruit fly, Drosophila melanogaster. Under ether anesthesia, the fly’s legs will shake ; even when the fly is unanaesthetized, it will exhibit aberrant movements. Sh-mutant flies have a shorter lifespan than regular flies; in their larvae, the repetitive firing of action potentials as well as prolonged exposure to neurotransmitters at neuromuscular junctions occurs.

Bertil Hille is an Emeritus Professor, and the Wayne E. Crill Endowed Professor in the Department of Physiology and Biophysics at the University of Washington. He is particularly well known for his pioneering research on cell signalling by ion channels. His book Ion Channels of Excitable Membranes has been the standard work on the subject, appearing in multiple editions since its first publication in 1984.

P2X purinoreceptor

The ATP-gated P2X receptor cation channel family, or simply P2X receptor family, consists of cation-permeable ligand-gated ion channels that open in response to the binding of extracellular adenosine 5'-triphosphate (ATP). They belong to a larger family of receptors known as the ENaC/P2X superfamily. ENaC and P2X receptors have similar 3-D structures and are homologous. P2X receptors are present in a diverse array of organisms including humans, mouse, rat, rabbit, chicken, zebrafish, bullfrog, fluke, and amoeba.

Voltage-gated potassium channel Class of transport proteins

Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state.

Two-pore channels (TPCs) are eukaryotic intracellular voltage-gated and ligand gated cation selective ion channels. There are two known paralogs in the human genome, TPC1s and TPC2s. In humans, TPC1s are sodium selective and TPC2s conduct sodium ions, calcium ions and possibly hydrogen ions. Plant TPC1s are non-selective channels. Expression of TPCs are found in both plant vacuoles and animal acidic organelles. These organelles consist of endosomes and lysosomes. TPCs are formed from two transmembrane non-equivalent tandem Shaker-like, pore-forming subunits, dimerized to form quasi-tetramers. Quasi-tetramers appear very similar to tetramers, but are not quite the same. Some key roles of TPCs include calcium dependent responses in muscle contraction(s), hormone secretion, fertilization, and differentiation. Disorders linked to TPCs include membrane trafficking, Parkinson's disease, Ebola, and fatty liver.

Voltage-gated proton channels are ion channels that have the unique property of opening with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such that their opening will only allow protons to leave cells. Their function thus appears to be acid extrusion from cells.

Channel blocker Molecule able to block protein channels, frequently used as pharmaceutical

A channel blocker is the biological mechanism in which a particular molecule is used to prevent the opening of ion channels in order to produce a physiological response in a cell. Channel blocking is conducted by different types of molecules, such as cations, anions, amino acids, and other chemicals. These blockers act as ion channel antagonists, preventing the response that is normally provided by the opening of the channel.

Gating (electrophysiology)

In electrophysiology, the term gating refers to the opening (activation) or closing of ion channels. This change in conformation is a response to changes in transmembrane voltage.

Acid-sensing ion channel Class of transport proteins

Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive sodium channels activated by extracellular protons permeable to Na+. ASIC1 also shows low Ca2+ permeability. ASIC proteins are a subfamily of the ENaC/Deg superfamily of ion channels. These genes have splice variants that encode for several isoforms that are marked by a suffix. In mammals, acid-sensing ion channels (ASIC) are encoded by five genes that produce ASIC protein subunits: ASIC1, ASIC2, ASIC3, ASIC4, and ASIC5. Three of these protein subunits assemble to form the ASIC, which can combine into both homotrimeric and heterotrimeric channels typically found in both the central nervous system and peripheral nervous system. However, the most common ASICs are ASIC1a and ASIC1a/2a and ASIC3. ASIC2b is non-functional on its own but modulates channel activity when participating in heteromultimers and ASIC4 has no known function. On a broad scale, ASICs are potential drug targets due to their involvement in pathological states such as retinal damage, seizures, and ischemic brain injury.

Clara Franzini-Armstrong is an Italian-born American electron microscopist, and Professor Emeritus of Cell and Developmental Biology at University of Pennsylvania.

KcsA potassium channel

KcsA (Kchannel of streptomyces A) is a prokaryotic potassium channel from the soil bacterium Streptomyces lividans that has been studied extensively in ion channel research. The pH activated protein possesses two transmembrane segments and a highly selective pore region, responsible for the gating and shuttling of K+ ions out of the cell. The amino acid sequence found in the selectivity filter of KcsA is highly conserved among both prokaryotic and eukaryotic K+ voltage channels; as a result, research on KcsA has provided important structural and mechanistic insight on the molecular basis for K+ ion selection and conduction. As one of the most studied ion channels to this day, KcsA is a template for research on K+ channel function and its elucidated structure underlies computational modeling of channel dynamics for both prokaryotic and eukaryotic species.

Ball and chain inactivation Model in neuroscience

In neuroscience, ball and chain inactivation is a model to explain the fast inactivation mechanism of voltage-gated ion channels. The process is also called hinged-lid inactivation or N-type inactivation. A voltage-gated ion channel can be in three states: open, closed, or inactivated. The inactivated state is mainly achieved through fast inactivation, by which a channel transitions rapidly from an open to an inactivated state. The model proposes that the inactivated state, which is stable and non-conducting, is caused by the physical blockage of the pore. The blockage is caused by a "ball" of amino acids connected to the main protein by a string of residues on the cytoplasmic side of the membrane. The ball enters the open channel and binds to the hydrophobic inner vestibule within the channel. This blockage causes inactivation of the channel by stopping the flow of ions. This phenomenon has mainly been studied in potassium channels and sodium channels.

References

  1. 1 2 "Book of Members, 1780-2010: Chapter A" (PDF). American Academy of Arts and Sciences. Retrieved April 25, 2011.
  2. ↑ "Clay M Armstrong, MD web page". Archived from the original on August 5, 2012. Retrieved February 27, 2012.
  3. ↑ "Function and structure of ion channels". laskerfoundation.org. Lasker Foundation. 1999. Retrieved August 28, 2022.
  4. ↑ "Gairdner - les prix Canada Gairdner awards". Archived from the original on April 4, 2012. Retrieved October 14, 2011.
  5. ↑ Adler, Elizabeth M. (2013). "Friends of Physiology: An Interview with Clara Franzini-Armstrong and Clay Armstrong". The Journal of General Physiology. 142 (5): 479. doi:10.1085/jgp.201311115. PMC   3813384 . PMID   24166877.
  6. ↑ Armstrong, C. M. (1969). "Inactivation of the Potassium Conductance and Related Phenomena Caused by Quaternary Ammonium Ion Injection in Squid Axons". The Journal of General Physiology. 54 (5): 553–575. doi:10.1085/jgp.54.5.553. PMC   2225944 . PMID   5346528.
  7. ↑ Armstrong, C. M.; Bezanilla, F (1974). "Charge movement associated with the opening and closing of the activation gates of the Na channels". The Journal of General Physiology. 63 (5): 533–552. doi:10.1085/jgp.63.5.533. PMC   2203568 . PMID   4824995.
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