Calcium-selective channels

Wissenbach, U., Niemeyer, B. A., Fixemer, T., Schneidewind, A., Trost, C., Cavalie, A., Reus, K., Meese, E., Bonkhoff, H. and Flockerzi, V., 2001, Expression of CaT-like, a novel calcium-selective channel, correlates with the malignancy of prostate cancer. J Biol Chem 276, 19461-8. 

S. Das, U. D. Lengweiler, D. Seebach and R. N. Reusch (1997). Proof for a nonproteinaceous calcium-selective channel by total synthesis from R-3-hydroxybutanoic acid and inorganic polyphosphate. Proc. Natl. Acad. Sci. USA, 94, 9075-9079. 

The ability of E. coli PHB/polyP complexes to form calcium-selective channels in planar bilayers was investigated in the planar bilayer system described above (Figure 5). E. coli DH5a cells were made genetically competent to increase the concentration of PHB/polyP in the membranes. Then vesicles were prepared from the cell envelopes, and added to the cis side of a planar bilayer formed by synthetic 16 0, 18 1 PC between symmetric bathing solutions of 250 mM CaCl2, 5 mM MgCl2,10 mM Tris Hepes, pH 7.3. The complexes were allowed to insert spontaneously into the bilayer.27 No activity was observed in the absence of an applied... 

Several calcium-selective channels have been described in different tisues, e.g. the N (present in neuronal tissue) and T (transient, found in brain, neuronal and cardiovascular tissue) the drugs discussed here selectively target the L channel for its cardiovascular importance. 

Das S, Lengweiler UD, Seebach D, Reusch RN (1997) Proof for a nonpro-teinaceous calcium-selective channel in Escherichia coU by total synthesis from (R)-3-hydroxybutanoic acid and inorganic polyphosphate. Proceedings of the National Academy of Sciences 94 9075—9079. 

Plasma membrane channels. The most common mechanism for the movement of into smooth muscle cells Ifom the extracellular space is the electrodiffusion of Ca " ions through highly selective channels. This movement can be significant in two quite different ways. First, Ca ions carry two positive charges and, in fact, most of the inward charge movement across the plasma membrane of smooth muscle myocytes is carried by Ca. Most smooth muscle action potentials are known to be Ca " action potentials. And second, the concentration of intracellular free calcium, the second messenger, is increased by inward calcium movement. 

The toxic mechanism of action of these various jellyfish venoms is complex. The cardiotoxic reaction seems to focus on calcium transport and is blocked by the prior or post administration of therapeutic doses of verapamil (7J). In neuronal tissue, Chrysaora venom induces large cationic selective channels which open and close spontaneously. These channels are permeable to Na , Li, K, and Cs but not and the channels are present in spite of the treatment with sodium and potassium inhibitors such as tetrodotoxin and tetraethylammonium (14). 

Calcium channels are a third major group of cation-selective channels.514 As pointed out in Box 6-D, calcium ions are involved in a very wide range of signaling functions. These are discussed in several places in this book. Several of these functions depend upon voltage-gated Ca2+ channels. Muscle is rich in L-type or DHP-sensitive channels (Box 6-D) which play a role in transmission of nerve impulses to muscles by allowing rapid flow of calcium ions into cells from outside.515... 

Zhuang, L., Peng, J. B., Tou, L., Takanaga, H., Adam, R. M., Hediger, M. A. and Freeman, M. R., 2002, Calcium-selective ion channel, CaTl, is apically localized in gastrointestinal tract epithelia and is aberrantly expressed in human malignancies. Lab Invest 82, 1755-64. 

The main target of cAMP is protein kinase A (PKA) which phosphorylates various proteins on Ser and Thr residues, for instance myosin light chain kinase in smooth muscles, or Cayl calcium channels in cardiac contractile cells. Beside PKA, cAMP can also bind to some other direct targets such as HCN cationic non-selective channels in cardiac pacemaker cells (see above). 

Agents which block calcium entry into secretory cells probably vary in effectiveness depending on the nature of calcium entry channels in surface membranes. It may be possible to develop calcium antagonists for selective inhibition of calcium entry into cells of a given secretory tissue. 

Acylpolyamines are potent neurotoxins that have been shown to inhibit calcium-ion channels and selectively block glutamate, NMDA (A-methyl-o-aspartate), or AMPA (a-amino-3-hydroxy-5-methylisoxazol-4-propionate) receptors, which is probably the basis of their insecticidal properties. As a result, acylpolyamines have received considerable attention as tools for studying neurotransmitter function and may be of therapeutic... 

A common function of S3 segments from calcium, sodium, and potassium channel proteins is suggested by the extensive sequence homology, particularly with respect to the position of negatively charged or polar residues that may be involved in lining a cation-selective channel. Four S3 segments may form a bundle of a-helices that create the transmembrane pore (4, 5, 37-39). 

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