Channel cations

Cations come in many shapes and sizes. The simplest is the lone proton which may jump from base to base along a small channel. Then there are inorganic ions with no directional preferences for bonding, such as the alkali or alkaline metals, and NH4+ which is tetrahedral but appears spherical when hydrated. At the other end of the spectrum of structural complexity we have organic cations and hydrated transition metal complexes with non-uniform charge densities. 

Four metal cations, Na+, K+, Mg2+ and Ca2+, are of primary importance. Na+ and K+ are ubiquitous in biological systems where they are employed to control membrane potential as well as intracellular levels of hydration. Several types of Na+ and K+ transporting channels are known to exist and some, notably the inwardly 

In 2007 the high resolution structure of an acid sensitive ion channel was obtained in the closed position at low pH [28], As shown in Fig. 5.11 the molecule is composed from three identical interlocking proteins and has a transmembrane region 

There are two main groups of transmembrane K+ channels the first includes proteins with six transmembrane domains such as the voltage-gated-K+ (Kv) channels and the Ca2+ activated-K+ (Kca) channel the second includes the inwardly 

Much more is known about the structure of Kir channels following the outstanding crystallographic work of MacKinnon s group to determine the structure of KcsA [5], which led to him sharing the 2003 Nobel Prize in chemistry. A theoretical model was devised by Bern che and Roux to analyse K+ movement through the KcsA selectivity filter in greater detail [32], KcsA also has much in common with Kv and Kca channels so aspects of the selectivity mechanism used by KcsA may well be found in other ion channels. 

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E. Hydrated divalent cation approaching a channel with a slightly larger diameter than in D, but the energy of interaction with the divalent cation is sufficient to deform the channel drawing the walls in to make lateral coordination with the divalent cation. Since the channel is too small for a monovalent cation to pass through with its first hydration shell and since the monovalent cation channel interaction is insufficient to make the channel small enough for lateral coordination of the monovalent cation, the channel is selective for divalent cations. (Part E reproduced with permission from Ref. 68 )... 

Like other voltage-gated cation channels, Ca2+ channels exist in at least three states A resting state stabilized at negative potentials (such as the resting potentials of most electrically excitable cells) that is a closed state from which the channel can open. The open state is induced by depolarization. Channels do not stay open indefinitely because they are turned off during prolonged depolarization by transition into an inactivated state. Inactivation is driven both by depolarization... 

IP3 Receptor Ryanodine Receptor Non-selective Cations Channels TRP Channels... 

Synthesized by soluble guanylyl cyclase and particulate guanylyl cyclase from guanosine triphosphate (GTP). Nitric oxide activates soluble guanylyl cyclase to enhance cyclic GMP production that contributes to various NO actions. Cyclic GMP is hydrolyzed by phosphodiesterases. Cyclic GMP binds to and activates cGMP-dependent protein kinase, phosphodiesterases, and Cyclic Nucleotide-regulated Cation Channels. 

Cyclic Nucleotide-regulated Cation Channels Cyclic Guanosine Monophosphate... 

Cyclic Adenosine Monophosphate Table Appendix Membrane Transport Proteins Cyclic Guanosine Monophosphate Non-Selective Cation Channels... 

Frere SGA, Kuisle M, Liithi A (2004) Regulation of recombinant and native hyperpolarization-activated cation channels. Mol Neurobiol 30 279-305... 

Nicotinic Receptors Voltage-dependent Na+ Channels Non-selective Cation Channels... 

Glutamate is a small amino acid which constitutes the most important neurotransmitter at excitatory synapses in the mammalian brain. Glutamate can act on several different types of receptors including cation channels and G-protein-coupled receptors. 

Inositol 1,4,5-trisphosphate (IP3) receptors are intracellular cation channels. They are expressed in most cells and predominantly within the membranes of the endoplasmic reticulum. They mediate release of Ca2+ from intracellular stores by the many receptors that stimulate IP3 formation. 

Ionotropic Glutamate Receptors Nicotinic Receptors Non-selective Cation Channels K+ Channels... 

Non-selective cation channels are macromolecular pores in the cell membrane that form an aqueous pathway. These enable cations such as Na+, K+ or Ca++ to flow rapidly, as determined by their electrochemical driving force, at roughly equal rates (>107 cations per channel pore and per second). 

The open channel has in most cases a selective permeability, allowing a restricted class of ions to flow,for example Na+, K+, Ca++ or Cl- and, accordingly, these channels are called Na+-channels, K+-channels, Ca -channels and Cr-channels. In contrast, cation-permeable channels with little selectivity reject all anions but discriminate little among small cations. Little is known about the structures and functions of these non-selective cation channels [1], and so far only one of them, the nicotinic acetylcholine receptor (nAChR, see Nicotinic Receptors), has been characterized in depth [2, 3]. The nAChR is a ligand-gated channel (see below) that does not select well among cations the channel is even permeable to choline, glycine ethylester and tris buffer cations. A number of other plasma... 

Non-selective Cation Channels. Figure 1 The nicotinic acetylcholine receptor (nAChR) is localized within the cell membrane above the cell membrane is the synaptic cleft, below the cytoplasm. Drawing of the closed (left) and open (right) nAChR showing acetylcholine (ACh) binding and cation movement. Dimensions of the receptor were taken from references [2, 3]. 

PKD2, also called polycystin 2, is a TRP-related protein defective in human autosomal polycystic kidney disease, the most common life-threatening genetic disease. PKD2 appears to be a cation channel in the plasma membrane, although there is evidence that it is an intracellular Ca2+release channel. Mammalian homologs include polycystin-like (PCL). 

P2X X CM CL Smooth muscle, platelets, cerebellum, dorsal horn spinal neurons a, 3-meATP = ATP = 2-MeSATP, L-p.y-meATP (rapid desensitization) TNP-ATP, lp5l, NF023, NF449 Intrinsic cation channel (Ca2+ and Na+)... 

P2X3 Sensory neurones, NTS, some sympathetic neurons 2-MeSATP>ATP>a,p-meATP>Ap4A (rapid desensitization) TNP-ATP, PPADS, A317491, NF110, lp5l, phenol red Intrinsic cation channel... 

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