Blocking events

To prepare a-saxitoxinol, saxitoxin was reduced with sodium borohydride and purified by chromatography on IRP-64 and Bio-Gel P2 (14,22,23). Current records from single-channel experiments using this material are shown in Figure 13. Note the absence of blocking events with long dwell times that would indicate the presence of residual saxitoxin. 

The subsequent records in Figure 12 are for saxitoxin derivatives bearing a 21-sulfo group (Bl, 2), an 11-a-hydroxysulfate (GTX2, 3), and both substituents (Cl, 4). Note the difference in the dwell times of the blocking events, in particular the great reduction in dwell time associated with the presence of the 21-sulfo group. 

Tamplin et. al. (54) observed that V. cholerae and A. hydrophila cell extracts contained substances with TTX-like biological activity in tissue culture assay, counteracting the lethal effect of veratridine on ouabain-treated mouse neuroblastoma cells. Concentrations of TTX-like activity ranged from 5 to 100 ng/L of culture when compared to standard TTX. The same bacterial extracts also displaced radiolabelled STX from rat brain membrane sodium channel receptors and inhibited the compound action potential of frog sciatic nerve. However, the same extracts did not show TTX-like blocking events of sodium current when applied to rat sarcolemmal sodium channels in planar lipid bilayers. 

The use of AR inhibitors to ameliorate the tragic consequences of long-term diabetes look promising from a biochemical and early clinical viewpoint. However, the pathological processes involved are complex and probably only partially understood at this time. Results of short trials to assess the value of drugs to block events that take a decade or more to develop have to be viewed with great caution. 

In addition to a normal role in movement of molecules across the mitochondrial outer membrane, VDACs appear to have roles in processes leading to cell death. These roles are influenced by proteins that bind to the VDACs. By forming a component of the mitochondrial permeability transition pore, VDACs may contribute to events leading to cell necrosis. Alternatively, binding of pro-apoptotic or anti-apoptotic members of the Bcl-2 family may change the permeability of the outer membrane so as to either favor or block events leading to programmed cell death (apoptosis). 

E.N. Ervin, R. Kawano, R. White, and H.S. White, "Simultaneous alternating and direct current readout of protein ion channel blocking events using glass nanopore membranes," And. Chem., vol. 60, no. 6, pp. 2069-2076, Jan. 2008. 

FIGURE 8.23 Highlighted features found in chronoamperograms for adsorption of 310 nm diameter silica spheres at a 2 pm Pt UME in 2.5 mM FcMeOH (a) desorption of a particle, with 50 fM silica spheres and 1 mM KCl (b) blocking events suggesting movement of one particle, with 5 fM silica spheres and 1 mM KCl (c) apparent instability of one or more adsorbed particles on the electrode, with 50 fM silica spheres and 5 mM KCl. (Reprinted by permission of ACS.)... 

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