Intracellular ionic concentrations

Fig. 14. The cellular ionic environment depicting representative intracellular ionic concentrations and the equiUbrium potentials, for individual ions. Excitatory and inhibitory events are represented by — and +, respectively. Thus, K" channel agonists and antagonists are inhibitory and excitatory, respectively Ca " channel antagonists and activators are inhibitory and excitatory, respectively.

Morelle, B. Salmon, J. M. Vigo, J. Viallet, P. Are intracellular ionic concentrations accessible using fluorescent probes The example of Mag-indo-1. Cell Biol. Toxicol. 1994, 10, 339-344. 

The plasma membrane Na+/Ca2+ exchanger is a high-capacity and low affinity ionic transporter that exchanges three Na+ ions for one Ca2+ ion. When intracellular Ca2+ concentrations [Ca2+]i rise and the... 

Several other conditions can provoke this reverse pump type of release. One is when the transmembrane ionic gradient is reversed. Experimentally this is achieved by reducing extracellular Na+. Because the neuronal uptake of monoamines from the synapse by the transporter requires co-transport of Na+ and Cl , reversing the ionic gradient (so that the Na+ concentration is lower outside, than inside, the terminals) will drive the transporter in the wrong direction. Such carrier-mediated release could explain the massive Ca +-independent release of noradrenaline during ischaemia which increases intracellular Na+ concentration and reduces intracellular K+. 

The generation of action potentials by muscle and nerve results from changes in the conductance of their membranes to sodium and potassium, and normal neuromuscular function depends on the maintenance of the correct ratio between intracellular and extracellular ionic concentrations. 

Cu is normally found at relatively high levels in the brain (100-150 xM) with substantial variations at the cellular and subcellular level [55-57]. Ionic Cu is compartmentalized into a post-synaptic vesicle and released upon activation of the NMDA-R but not AMPA/kainate-type glutamate receptors [58]. The Menkes Cu7aATPase is the vesicular membrane Cu transporter, and upon NMDA-R activation, it traffics rapidly and reversibly to neuronal processes, independent of the intracellular Cu concentration [58]. Cu ions function to suppress NMDA activation and prevent excitotoxicity by catalyzing S-nitrosylation of specific cysteine residues on the extracellular domain of the NRl and NR2A subunits of the NMDA receptor [58]. The concentrations of Cu in the synaptic cleft can reach approximately 15 xM. Subsequently, Cu is cleared by uptake mechanisms from the synaptic cleft. Several studies have shown that Cu levels increase with age in the brains of mice [22-24]. 

The extracellular fluid of animal cells has a salt concentration similar to that of sea water. However, cells must control their intracellular salt concentrations to prevent unfavorable interactions with high concentrations of ions such as calcium and to facilitate specific processes. For instance, most animal cells contain a high concentration of K and a low concentration of Na" " relative to the external medium. These ionic gradients are generated by a specific transport system, an enzyme that is called the Na -K pump or the... 

In conclusion, normally, low concentrations of palytoxin are sufficient to produce a massive increase in the permeability of cells to cations. Palytoxin stimulates sodium influx and potassimn efflux, and thus produces depolarization of the membrane in several cellular systems. In excitable systems, palytoxin-stimiflated depolarization can modulate calcium channel activity, resulting in a rise in the intracellular calcimn concentration, which can afterwards regulate calcium-dependent pathways and their related events. In muscle, depolarization causes calcium release and contraction. In vivo, the depolarization caused by the toxin can produce vasoconstriction, which can be lethal. In other systems, palytoxin-regulated events may not require an increase in the intracellular calcimn concentration. Whether the high cytotoxicity of palytoxin is merely a consequence of its disruption of the ionic enviromnent of the cell remains to be elucidated. 

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