Cation influx

Although Ca2+ only carries a small proportion of currents through cell membrane-inserted a-LTX channels (Hurlbut et al. 1994 Tse and Tse 1999), the influx of Ca2+ through presynaptically-targeted a-LTX channels is most often referred to, because of the well-established link between presynaptic [Ca2+] and neurotransmitter release. There is a wealth of evidence indicating that in conditions favorable to channel formation (e.g., in the presence of divalent cations), influx of extracellular Ca2+ through a-LTX channels is an important aspect of a-LTX action. 

Rulon LL, Robertson JD, Lovell MA, Deibel MA, Ehmann WD, Markesber WR (2000) Serum zinc levels and Alzheimer s disease. Biol Trace Elem Res 75 79-85 Samudralwar DL, Diprete CC, Ni BF, Ehmann WD, Markesbery WR (1995) Hemenfeil imbalances in the olfactory pathway in Alzheimer s disease. J Neurol Sci 130 139-145 Segal D, Ghana E, Besser L, Hershfinkel M, Moran A, Sekler I (2004) A role for ZnT-1 in regulating cellular cation influx. Biochem Biophys Res Commun 323 1145-1150... 

HPTS is a pH-sensitive fluorophore (pk, 7.3) [6]. The opposite pH sensitivity of the two excitation maxima permits the ratiometric (i.e. unambiguous) detection of pH changes in double-channel fluorescence measurements. The activity of synthetic ion channels is determined in the HPTS assay by following the collapse of an applied pH gradient. In response to an external base pulse, a synthetic ion channel can accelerate intravesicular pH increase by facilitating either proton efflux or OH influx (Fig. 11.5c). These transmembrane charge translocations require compensation by either cation influx for proton efflux or anion efflux for OH influx, i.e. cation or anion antiport (Fig. 11.5a). Unidirectional ion parr movement is osmotically disfavored (i.e. OH /M or X /H symport). HPTS efflux is possible with pores only (compare Fig. 11.5b/c). Modified HPTS assays to detect endovesiculation (Fig. 11.1c) [16], artificial photosynthesis [17] and catalysis by pores [18] exist. 

Furthermore, the uptake of Na occurred simultaneously with the onset of shape change and aggregation (37 39 40). On the other hand, epinephrine-induced aggregation, shown earlier to induce 4 Ca + uptake, had no effect to induce Na uptake (Figure 5) (3 ,40). Consequently it appears that cation influx is agonist specific, at least with respect to activation by ADP or by epinephrine. 

With prolonged or repeated exposure to capsaicin (3), however, one will eventually beeome insensitive to its effects as excessive cation influx leads to death of the neurons. It is for this reason that people can cultivate a toleranee for spicy food over time, enabling some to have the ability to eat peppers so hot that their mere smell would make the eyes of those less accustomed water profusely. The perhaps more significant feature is this desensitization suggests that capsaicin could serve as an analgesic to mitigate the pain and inflammation associated with several disorders such as... 

Mehta, D.C., Short, J.L., Nicolazzo, J.A., 2013. Memantine transport across the mouse blood-brain barrier is mediated by a cationic influx antiporter. Mol. Pharmaceut. 10, 4491-4498. 

It seems that this anionic exchange would be relevant also to explain interactions of trialkyl tin (TAT) compounds (TET, tripropyltin chloride, TBT chloride) with the mitochondria. The current view of this phenomenon is that these compounds, by exploiting the Cl and OH gradient in energized mitochondria, behave as electroneutral OH /Cl exchangers. The crucial point of this new mechanism is that TATs enter the mitochondria as lipophilic cations [RsSn (rV)] and not as electroneutral compounds. The influx is followed by extrusion of the TAT compounds as electroneutral hydroxy compounds RsSnOH. ... 

In the present experiments, MTX markedly increased the tissue Ca content, Ca uptake, and intracellular free Ca concentration of smooth or cardiac mus cles. These Ca -mobilizing effects of MTX as well as its vasoconstrictive, cardio tonic, and cardiotoxic effects were profoundly suppressed or abolished by Ca entry blockers, polwalent cations, or Ca -free medium. It has been reported that MTX produces Ca -dependent excitatory effects on neuronal (10,11,18) or pituitary (26) cells and smooth (12,13), cardiac (14,15,17), or skeletal (16) muscles, and that all these actions of MTX were antagonized by Ca antagonists or polyvalent cations. These observations suggest that the enhanced Ca influx and the subsequent increase in cytoplasmic free Ca concentration play a dominant role in the excitatory effects of MTX. 

Evidence from a number of systems suggests that ion flux plays a role in palytoxin action. In a wide range of systems, palytoxin effects are accompanied by a change in intracellular cation levels. For example, the influx of Na and/or Ca is associated with palytoxin-stimulated contraction of cardiac and smooth muscle, the release of norepinephrine by rat pheochromocytoma (PC12) cells, and the depolarization of excitable membranes 12—15). Palytoxin also induces K efflux from erythrocytes and thus alters ion flux in a nonexcitable membrane system as well 16-19). In both excitable and nonexcitable membranes, the ultimate action of palytoxin has been shown to be dependent on extracellular cations. The palytoxin-induced effects on smooth muscle and erythroctyes can be inhibited by removing Ca from the media, and the palytoxin-induced release of norephinephrine from PC12 cells can be blocked in Na" free media (ii, 14y 18, 20, 21)... 

The cyclic-nucleotide-gated channel is permeable to cations, especially Ca2+. Thus, increased channel activation results in influx of Ca2+ and a transient rise in the intracellular Ca2+ concentration. Intracellular Ca2+ concentrations of 1-3 J,M have been found to lead to a decrease in the open probability of the ion channel, even... 

The molecules that transduce noxious heat or cold are members of the transient receptor potential (TRP) receptor family. TRP proteins (Table 57-2) form tetra-meric nonselective cation channels within the plasma membrane, allowing sodium and calcium ion influx [4]. The TRPV3 channel is activated at temperatures between 31 and39°C, TRPV1 at43°C, and TRPV2 at 52-55°C. The heat pain threshold in humans is 43°C, suggesting that... 

TRP6-specific antisense oligonucleotides, and consequently, cationic current and Ba2+ influx evoked in response to oq -adrenoceptor activation were both greatly attenuated. Importantly, Ba2+ influx induced by thapsigargin, which is an indication of store operated divalent cation entry, was not significantly affected... 

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