Transport transmembrane channels

Urry, D. W. On the Molecular Structure and Ion Transport Mechanism of the Gramicidin Transmembrane Channel. In Membranes and Transport, Vol. 2, (ed. Martonosi, A.), p. 285, Plenum Publishing Corporation, New York 1982... 

The binding of PCP to its receptor initiates a series of coupled neurochemical events eventually leading to the expression of behavior. One such coupling reaction was described by BLAUSTEIN as a blockade of transmembrane channels that transport K+ into the neuronal cells. Since K+ movements are part of the process of neurotransmission between neurons, this effect of PCP may explain the results of studies by MARWAH and by JOHNSON, in which several neurotransmitter systems were shown to be involved in the actions... 

The following conditions must be fulfilled in the ion transport through an ion-selective transmembrane channel ... 

The bonding of K+ and Na+ to A-methylacetamide is of interest64 in studies of the interaction of these ions with peptides and proteins, and particularly studies of the ion transport through transmembrane channels such as the gramicidin channel. Roux and Karplus35 have used the complexation of the given alkali ion with two N-methylacetamide molecules and two water molecules as a model for interactions occurring in transmembrane channels. 

The 12-transmembrane-spanning domain topology of the adenylyl cyclase enzymes is similar to that found in the ABC family of transporters (see Ch. 5), which includes the cystic fibrosis transmembrane rectifier and the P-glyco-protein. However, there is currently no convincing evidence of a transporter or channel function for mammalian adenylyl cyclases. The structural similarity may indicate that these functionally divergent protein families are derived in an evolutionary sense from related proteins. 

The peptide subunit was easily incorporated into lipid bilayers of liposome, as confirmed by absorption and fluorescence spectroscopy. Formation of H-bonded transmembrane channel structure was confirmed by FT IR measurement, which suggests the formation of a tight H-bond network in phosphatidylcholine liposomes. Liposomes were first prepared to make the inside pH 6.5 and the outside pH 5.5. Then the addition of the peptide to such liposomal suspensions caused a rapid collapse of the pH gradient. The proton transport activity was comparable to that of antibiotics gramicidin A and amphotericin B. 

Satisfaction of kinetic order. Carriers follow Michaelis-Menten-type saturation kinetics or first-order kinetics. Ion channels follow the type of respective structure—unimolecular transmembrane channels and bimolecular half-channels follow first- and second-order kinetics, respectively. The kinetic order of supramolecular channels depends on the assembly number. However, this principle can be applied only when the association constants are small. If the association becomes strong, the kinetic order decreases down to zero. Then the validity becomes dubious in view of the absolute criterion of the mechanism. Decreased activation energy compared to the carrier transport mechanism and competitive inhibition by added other cations stand as criteria. 

The chemistry of transport systems has three main goals to design transport effectors, to devise transport processes, and to investigate their applications in chemistry and in biology. Selective membrane permeability may be induced either by carrier molecules or by transmembrane channels (Fig. 10). 

Transmembrane channels represent a special type of multi-unit effector allowing the passage of ions or molecules through membranes by a flow or site-to-site hopping mechanism. They are the main effectors of biological ion transport. Natural and synthetic peptide channels (gramicidin A, alamethicin) allowing the transfer of cations have been studied [6.66-6.68]. 

Ions and small molecules may be transported across cell membranes or lipid bilayers by artificial methods that employ either a carrier or channel mechanism. The former mechanism is worthy of brief investigation as it has several ramifications in the design of selectivity filters in artificial transmembrane channels. To date there are few examples where transmembrane studies have been carried out on artificial transporters. The channel mechanism is much more amenable to analysis by traditional biological techniques, such as planar bilayer and patch clamp methods, so perhaps it is not surprising that more work has been done to model transmembrane channels. 

Successful synthetic transmembrane channels must have three characteristics if they are to replicate the behaviour of natural systems. They must span the cell membrane, implying a single molecule or stable self-assembled complex over 4 nm in length. Ideally they should also be able to discriminate in favour of one chemical species, if they are to mimic the highly selective channels, and transport that species at rates in the region of 104 to 108 ions per second to match the efficacy of natural channels. 

In this review, we first discuss the individual properties of polyPs and PHBs related to their function in ion transport, and then consider how these two structurally dissimilar polymers may act in synergy to form ion-selective transmembrane channels. Finally, we examine protein ion transporters that contain PHBs and polyPs, and consider how these three macromolecules may come together in supramolecular channels to refine ion recognition and regulate ion transport. 

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