Rapid influx

The ventricular action potential is depicted in Fig. 6-2.2 Myocyte resting membrane potential is usually -70 to -90 mV, due to the action of the sodium-potassium adenosine triphosphatase (ATPase) pump, which maintains relatively high extracellular sodium concentrations and relatively low extracellular potassium concentrations. During each action potential cycle, the potential of the membrane increases to a threshold potential, usually -60 to -80 mV. When the membrane potential reaches this threshold, the fast sodium channels open, allowing sodium ions to rapidly enter the cell. This rapid influx of positive ions... 

We and others have demonsttated that an endothelial, cell surface protein-disulfide isomerase-mediated mechanism, does exist for the rapid influx of RSNO bound-NO (Zai et al. 1999 Ramachandran et al., 2001). Whether the csPDI route plays a role in the transfer of NO-equivalents from RBCs remains to be answered. 

While all of these events are interconnected, the two most critical are neuronal rapid influx of Ca2+ and activation of nNOS, both which trigger all downstream events. Therefore, directly blocking the toxic effects of glutamate /NO, can be achieved through many means, including selective nNOS inhibitors, Ca2+ channel blockers [NMDA, Kainate/AMPA] [ryanodine-sensitive, IP3], calmodulin antagonists, Ca2+... 

In the laboratory experiments of Seyfried et al. (1998), naturally altered sea floor basalt (5 Li = +7.4) was reacted with Li-free alkali-chloride aqueous fluid at 350°C for 890 hours (initial fluid/solid mass ratio 2). Samples of the fluid were taken throughout the experiment, and showed initial rapid influx of isotopically heavy-enriched Li released by early-dissolving alteration minerals. However, with progressive reaction, isotopic composition of the fluid decreased and Li concentration reaehed apparent steady state. Although an equilibrium model applies best to the synthetic results, Rayleigh distillation was considered most likely to apply in hydrothermal reactions occurring in nature. 

At this time, the proposal of additional access channels is quite conjectural. It seems likely that there is a channel or access route to the proximal side of the heme in order to provide access for the hydrogen peroxide or water needed for heme oxidation and His-Tyr bond formation. Furthermore, the electron density of compoimd I from PMC (97) reveals the presence of an anionic species that is not present in the native enz5une. However, the rapid influx-efflux rates up to 10 per sec needed for such a species to be a component of compoimd I would pose interesting constraints on a channel, and there does not seem to be a likely candidate in the region. Similarly, the potential channel leading to the cavity at the molecular center is not an ideal candidate for substrate or product movement because of its relationship to the active site residues. However, if the lateral channel is truly blocked by NADPH in small-subunit enzymes, this route may provide an alternative access or exhaust route. Both of these latter two channels require further investigation before a clear role can be ascribed to them. 

Arrival of the nerve impulse at a nerve terminal leads to the opening of voltage-gated Ca2+ channels and rapid influx of Ca2+. The increase in Ca2+ concentration at the active zone from a basal level of 100 nM to more than 200 pM results in an appropriate neurotransmitter release within 200 ps (Barrett and Stevens, 1972 Linas et al., 1981 1992 Augustine and Neher, 1992 Zucker, 1993 Heidelberger et al., 1994). 

Details of the control of exocytosis are also uncertain. Synaptotagmin I, which contains two Ca2+-binding domains, is probably the sensor that detects the rapid influx of Ca2+ that initiates exocytosis.576 578b... 

The only internationally used drug effective for treating schistosomiasis is praziquantel. This drug induces a rapid influx into the worms of surrounding Ca2+, a process that leads to paralysis (Martin, 1997), and changes in the surface membrane architecture that lead to the exposure of worm antigens that are normally cryptic (Brindley and Sher, 1987). Parasites affected in this way become susceptible to antibody-mediated immune attack and are killed as a result of the synergistic actions of chemotherapy and the immune response (Doenhoff et al., 1987 Brindley etal., 1989). 

One of the early responses made by many types of cells to a stimulus is a rapid influx of calcium ions across the plasma membrane and a resulting increase in the cytoplasmic level of free ionic calcium. 

There are three important ADP receptors on the platelet surface (16). The P2X, inotrophic receptor is responsible for rapid influx of calcium into the cytosol. The P2Y, receptor mediates mobilization of calcium through activation of PLC and shape change. The P2Y,2 receptor is coupled to adenyl cyclase inhibition mediated by a G-protein with subsequent decrease in the cAMP The decrease in cAMP stimulates dephosphorylation of VASP that is closely correlated with the GPIIb/llla activation. 

As the action potential sweeps into presynaptic region, there is a rapid influx of calcium from the extra cellular fluid into a qtecialized area of the presynaptic terminus termed the maptic knob. Via the process of exocytosis, specific neurotransmitters are then released from synaptic vesicles into the synaptic gap. The neurotransmitters drfiuse across the synaptic gap and specifically bind to specialized receptor sites cn the dendrite of the post aptic neurcn. 

Purkinje cells is demonstrated in Figure 12.1 and, like all cardiac myocytes, can be divided into four phases. Phase 4 (pacemaker potential) involves the slow influx of sodium ions, depolarizing the cell until the threshold potential is reached. Once the threshold potential is reached, the fast sodium current is activated, resulting in a rapid influx of sodium ions causing cell depolarization (phase 0 rapid depolarization). Phase 1 (partial repolarization) involves the inactivation of sodium channels and a transient outward current. Phase 2 (plateau phase) results from the slow influx of calcium ions. Repolarization (phase 3) occurs as a result of outflow of potassium ions from the cell and restores the resting potential. There are variations between the different areas of the heart, specifically the nodal tissues do not possess fast sodium channels and slow L-t5rpe calcium channels generate phase 0 current (Fig. 12.1). Phase 4 activity varies between nodal areas the sinoatrial node depolarizes more rapidly than the atrioventricular (AV) node. Automaticity is under autonomic nervous system control. Parasympathetic neurons... 

In a study of the absorption of inorganic mercury by the rat jejunum, Foulkes and Bergman (1993) found that while tissue mercury could not be rigorously separated into membrane-bound and intracellular compartments (as can the heavy metal cadmium), its uptake into the jejunum includes a relatively temperature-insensitive and rapid influx into a pool readily accessible to suitable extracellular chelators. A separate, slower and more temperature-sensitive component, however, leads to the filling of a relatively chelation-resistant compartment. Nonspecific membrane properties, such as surface charge or membrane fluidity, might account for mucosal mercury uptake (Foulkes and Bergman 1993). 

Calcium ion channels. Immediately after the Na+ pores open as a result of membrane depolarization, voltage-sensitive Ca + channels also open. These allow a rapid influx of Ca +, which can trigger many processes including the secretion of neurotransmitters within the synapses. There are several types of volfage-sensifive Ca + channels. The most abundant type are specifically inhibifed by dihydropy-ridines and are called dihydropyridine-sensitive or L-type channels. They are most numerous in the transverse tubular membranes of skeletal muscle where they appear to form a complex with the very large calcium release channels, the ryanodine receptors (Fig. 19-21 and associated discussion). ... 

Studies on sugar and amino acid uptake by L. donovani promastigotes revealed that addition of D-glucose or L-proline caused a rapid influx of protons into these cells, indicating that both substrates are co-transported with protons (52). This active transport system involves a proton-motive force (pmf)-driven mechanism which requires the maintenance of a proton electrochemical gradient. Such a gradient is composed of the chemical gradient (ApH) and the membrane potential (Ai/ ) (52). 

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