Transmembrane cation channels

It has been known for some years that gramicidin forms transmembrane ion channels in lipid bilayers and biological membranes and that these channels are assembled from two molecules of the polypeptide 213). The channels are permeable specifically to small monovalent cations [such as H+, Na+, K+, Rb+, Cs+, Tl+, NH4+, CHjNHj, but not (CH3)2NH2+J and small neutral molecules (such as water, but not urea). They do not allow passage of anions or multivalent cations 21 n. 

Sympathetic parasympathetic ganglia ACh Nicotine Trimethaphan Ganglionic type (o3p4) Nicotinic (N) cholinoceptor ligandgated cation channel formed by five transmembrane subunits muscular type (al2PlY5)... 

The mechanism of action of U ions remains to be fully elucidated. Oiemi-cally, lithium is the lightest of the alkaU metals, which include such biologically important elements as sodium and potassium. Apart from interference with transmembrane cation fluxes (via ion channels and pumps), a lithium effect of major significance appears to be membrane depletion of phosphatidylinositol bisphosphates, the principal lipid substrate used by various receptors in transmembrane signalling (p. 66). 

With the larger Ms(calix) crown (3.127),65 two dynamic processes are observed. The intermolecular association/disassociation equilibrium in which the complex equilibrates with the uncomplexed ligand and free metal cation is slow on the NMR time scale. The complex also exhibits a faster intramolecular vibration of the metal cation from one binding site to another (Scheme 3.26). Compound 3.127 is also interesting because the mechanism of this fast, intramolecular cation shuttling process may have important implications on the analogous movement of metal cations through transmembrane ion channels (Section 2.2). 

In addition to causing presynaptic depolarization, activation of presynaptic ionotropic receptors may provide another way of transmembrane Ca2+ entry in order to promote Ca2+-dependent vesicle exocytosis the Ca2+-permeable ionophores of transmitter-gated cation channels (Rogers and Dani 1995). In this latter case, Ca2+ entering the nerve terminal via an ionotropic receptor may bypass voltagegated Ca2+ channels and directly stimulate Ca2+-dependent vesicle exocytosis. If... 

Both intracellular release and transmembrane flux contribute to the rise in intracellular Ca2+.14,15 The rise in keratinocyte intracellular Ca2+ in response to raised extracellular Ca2+ has two phases (a) an initial peak, not dependent on extracellular Ca2+ and (b) a later phase that requires extracellular Ca2+.14 An early response of human keratinocytes to increases in extracellular Ca2+ is an acute increase in intracellular Ca2+. Stepwise addition of extracellular Ca2+ to neonatal human keratinocytes is followed by a progressive increase in intracellular Ca2+, where the initial spike of increased intracellular Ca2+ is followed by a prolonged plateau of higher intracellular Ca2+.16 The response of intracellular Ca2+ to increased extracellular Ca2+ in keratinocytes is saturated at 2.0 mM extracellular Ca2+.16,17 The response of intracellular Ca2+ to increased extracellular Ca2+ in keratinocytes resembles the response in parathyroid cells, in that a rapid and transient increase in intracellular Ca2+ is followed by a sustained increase in intracellular Ca2+ above basal level. This multiphasic response is attributed to an initial release of Ca2+ from intracellular stores followed by an increased influx of Ca2+ through voltage-independent cation channels. The keratinocyte and parathyroid cell contains a similar cell membrane calcium receptor thought to mediate this response to extracellular Ca2+. This receptor can activate the phospholipase-C pathway, leading to an increase... 

One of the characteristic motifs of heavy metal P-type ATPases is the CPX (commonly CPC) motif within transmembrane domain 6, widely regarded as a part of the cation channel (Silver and Phung, 1996) (Fig. 1). The possible role for these cysteines in the transmembrane domain may be the coordination of a heavy metal during its translocation through the cation channel. While these cysteines have proved to be essential for the function of some HMPAs, their exact role in catalysis is yet to be fully understood (Bissig et al., 2001 Forbes and Cox, 2000). 

P-type ATPases. This is an unexpected finding as generally the cation specihcity of P-type ATPases is restricted to the amino acid composition of cation channels in transmemhrane domains (Axelsen and Palmgren, 1998 Mpller et al., 1996). It is probable that other, as yet to be identihed, intramolecular interactions may be important for the specihc cation transport by heavy metal P-type ATPases. Cysteine residues in transmembrane domain 6, which form a characteristic CPx (commonly CPC) motif, are commonly regarded as core elements of the cation channel in CuPAs. However, there is no direct evidence to date to support that assumption. 

Each domain or subunit In voltage-gated cation channels contains six transmembrane a helices and a nonhelT cal P segment that forms the Ion-selectivity pore (see Figure 7-36). 

The nicotinic acetylcholine receptor, a ligand-gated cation channel, contains five subunits, each of which has a transmembrane a helix (M2) that lines the channel (see Figure 7-45). 

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