Ion channel pore

Leonard, R.J., Labarca, C.G., Chamet, P., Davidson, N., Lester, H.A. Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor. Science. 242 1578, 1988. 

Nicotine is an agonist at the nicotinic acetylcholine receptor (nAChR). Activation of this receptor depolarizes target cells (see Ch. 11). nAChRs are composed of five subunits surrounding a central ion-channel pore. Twelve different nicotinic receptor subunits are expressed in the nervous system (a2-oclO and (32—134). Of these, a subset is expressed in the VTA (a3-a7 and P2—134). It is thought that a7 receptors form homomeric receptors a3, a4 and a6 form heteromeric channels with 02 or 04 and a5 and 03 can associate with other a/0 pairs. Studies in knockout mice implicate several subunits in the ability of nicotine to modulate dopamine neurons (a4, a6, a7, 02, 03) but... 

Figure 5.8 Closed and opened views of the potassium ion channel pore according to reference 25. S4 helix of PDB lORQ. Visualized using CambridgeSoft ChemSD Ultra 10.0 with notations in ChemDraw Ultra 10.0. (Printed with permission of CambridgeSoft Corporation.) (See color plate)...

Figure 1.6 General structure of a ligand-gated ion channel. They are formed by 4-5 subunits each consisting of four membrane-spanning hydrophobic a helices that form the central ion channel pore.

The next essential feature of the model is the incorporation of the ionic conduction channels into the lattice structure. Radioactive ion tracer studies long ago [64] established a relative surface density of ion channel pores. It is possible to use these data to estimate that an average distance between channels should be about 100 A. As this distance is large, it is not easy to envisage a genuine, fast ionic conduction mechanism along the surface that contributes to the message... 

Selectivity filter— The narrowest region of an ion channel pore that determines which type of ion can pass through the channel. 

Water is considered to diffuse through membranes by unspecific movement through ion channels, pores, or around proteins embedded in the lipids. Certain cells (e.g., renal tubule cells) also contain large protein pores, called aquaporins, which permit a high rate of water flow from a region of a high water concentration (low solute concentration) to one of low water concentration (high solute concentration). 

Kashiwagi, K Masuko, T., Nguyen, C. D., Kuno, T., Tanaka. I., IgarashI, K., and Willianus. K. (2002), Channel blockers acting at vV-nicthyl-D-aspartaie receptors Differential effects of mutations in the vestibule and ion channel pore. Mol. Pharmacol. 61,533-545. 

Outline the possible role of the 55 and 56 segments of sodium, potassium, and calcium channels as a key region of the ion channel pore. 

However, ion carrier activity in the U-tube does not exclude the possibility that the same molecule or supermolecule can also function as ion channel, pore, or detergent in lipid bilayer membranes (and vice versa). 

Fig. 2 A schematic of the proposed molecular structure of the Na channel present in the heart. This model depicts the transmembrane folding of the primary structure of the Na channel a-subunit. The domains of the channel are indicated as DI-DIV. The six a-helical transmembrane-spanning sequences are indicated as S1-S6 for the DI domain. Some experimentally determined sites for protein kinase A phosphorylation and local anaesthetic binding are shown. Those sequences involved in channel inactivation are also indicated along with those regions that constitute the ion channel pore (P)...

Chernenko has investigated the effect of a counterion-induced dielectric decrement on the solution of the Gouy-Chapman equation. Sansom et al. have studied the effect of a local dielectric coefficient in an ion channel pore (in the absence of ions), and others have analyzed cylindrical models of Kozak and co-workers and Frahim and Diekmann have... 

Pig. 20.1 Schematic showing the structure of NMDA receptor subunits. NMDA receptors are tetramers, with the M2 region of each subunit contributing to the channel pore. Portions of the Ml, M3, and M4 domains also form part of the ion channel pore and vestibule... 

---