Channel ionic

B Hille. Ionic Channels of Excitable Membranes. 2nd ed. Sunderland, MA Smauer, 1992. 

It is possible that the stationary-state situations leading to an active ion transport occur only in localized regions of the membrane, i.e., at ATPase molecule units with diameters of about 50 A and a length of 80 A. The vectorial ion currents at locations with a mixed potential and special equipotential lines would appear phenomenologically like ionic channels. If the membrane area where the passive diffusion occurs is large, it may determine the rest potential of the whole cell. 

Antiarrhythmic drugs are substances that affect cardiac ionic channels or receptors, thereby altering the cardiac action potential or its generation or propagation. This results in changes of the spread of activation or the pattern of repolarization. Thereby, these drugs suppress cardiac arrhythmia. 

Antiarrhythmic treatment is based upon modulation of the ionic currents mentioned above. A principal problem with this therapy is that the electrophysiology of all cells is targeted and not specifically the arrhythmogenic focus. As a consequence, all antiar-rhythmics acting at transmembrane ionic channels possess a risk for elicitation of arrhythmia (= proar-rhythmic risk). 

Hille B (1992) Ionic channels of excitable membranes. Sinauer Associates, Sunderland, pp 1-423... 

The axonal membrane is a lipid bilayer in the nerve fibre. Ionic channels and other proteins are located in the membrane to achieve electrical activity. Action potentials are generated and conducted along the membrane. 

An increase in [Na+]j can also regulate the Na+/Ca2+ exchanger. In particular, when intracellular Na+ increases, it binds to the transport site of the exchanger molecule, and after this Na+ influx, an inactivation process of the exchanger occurs. This inactivation process, very similar to the phenomenon occurring in voltage-dependent ionic channels, is named... 

State-dependent block describes the binding of a drug to a certain state of an ionic channel. Tims, the fast Na+ channel switches between a resting and open and inactivated states, the latter being the state to which antiarrhythmic drugs like lidocaine bind. 

Hartshome, D.J. (1987). Biochemistry of the contractile process in smooth muscle. In Physiology of the Gastrointestinal Tract. 2nd Edition (Johnson. L.R. ed.), pp. 423-482, Raven Press, New York. Hille, B. (1992). Ionic Channels of Excitable Membranes. 2nd edn., Sinauer Associates, Sunderland, MA. 

Ca may activate phospholipase A2 and cause production of lyso-lipids and fatty acids. In addition, ionic fluxes across the membrane occur, leading to pH changes and membrane depolarization. It is not clear how these other responses are initiated, but there may be direct G-protein links to effector systems such as phospholipase A2 or ionic channels. 

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

Hille, B. Ionic Channels of Excitable Membranes Sinauer Associates Sunderland, MA, USA, 1984. 

It is necessary for two molecules of agonist (A) to bind to the receptor (R) in order to initiate a conformational shift from Jhe closed ion channel configuration (A2R) to the open channel configuration (A2R ). In mature muscle the open ionic channel has a conductance of 30-32 pS this is a constant property of the receptor. [A lower conductance state occurs with receptors found in immature or denervated muscles (24—26).] The properties which depend upon the agonist are the rates of binding and dissociation and the rates at which conformational shifts occur. 

In other chapters of this volume considerable attention is given to marine toxins whose cellular sites of action have been identified. For example, saxitoxin, brevetoxin, and sea anemone toxins are prototypes of toxic molecules whose chemical structure is known, and whose actions on ionic channels in the cell membrane have been elucidated. Recent additions to such toxins are the piscivorus cone... 

Hille, B. (1984) Ionic Channels in Excitable Membranes, Sinauer, Sunderland, MA. 

H, and Albuquerque, E.X. Interaction of phencyclidine and its analogues on ionic channels of the electrically excitable membrane and nicotinic receptor Implications for behavioral effects. Mai Pharmacol 21 637-647, 1982. 

Eldefrawi, A.R. and Eldefrawi, M.E.. Phencyclidine interactions with the ionic channel of the acetylcholine receptor and electrogenic membrane. Proc Natl Acad Sci USA 77 1224-1228,... 

Ulbricht, W., Ionic channels and gating currents in excitable membranes, Ann. Rev. Biophys. Bioeng., 6, 7 (1977). 

Figure 1 Schematic diagrams illustrating the patch-clamp technique. (A) Overall setup for isolating single ionic channels in an intact patch of cell membrane. P = patch pipet R = reference microelectrode I = intracellular microelectrode Vp = applied patch potential Em = membrane potential Vm = Em — Vp = potential across the patch A = patch-clamp amplifier. (From Ref. 90.) (B) Five different recording configurations, and procedures used to establish them, (i) Cell attached or intact patch (ii) open cell attached patch (iii) whole cell recording (iv) excised outside-out patch (v) excised inside-out patch. Key i = inside of the cell o = outside of the cell. (Adapted from Ref. 283.)...

Aguayo, G., Wamick, J. E., Maayani, S., Glick, S. D., Weinstein, H., and Albuquerque, E. X. (1982) Site of action of phencyclidine. V. Interaction of phencyclidine and its analogues on ionic channels of the electrically excitable membrane and nicotinic receptor Implications for behavioral effects. Mol. Pharmacol., 21 637-647. 

Eisenberg, B. (1998). Ionic channels in biological membranes natural nanotubes, Acc. Chem. Res., 31, 117-123. 

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