Ionic Current through Protein Pores

The experimentally observed current-voltage curves for protein channels can be quite complicated, instead of the simple Ohmic behavior (Aidley and Stanfield 1996, Hille 2001). These complications arise from the rich decoration of both positive and negative charges on the ionizable amino acid groups on the irregularly shaped internal interfaces of the pore. It is difficult to monitor the electric potential variations and the distributions of the mobile cations and anions along 

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In the steady state, when the drift contribution dominates, the ionic current obeys the Ohm s law. In the absence of either drift or barriers, the behavior of ions is according to the Pick s law. The GHK equations offer a convenient way to describe the crossover behavior between the diffusion-, drift-, and barrier-dominated regimes. We have also shown the utility of the numerically solved results from the PNP equations for the ionic currents through the GA channel and the aHL protein pore. The PNP calculations show that the steepest gradient in the electrical potential is only very near and across the pore. We have... 

Fig. 15 (a) DNA translocation through a protein pore in a-hemolysin. When the DNA enters the pore, the ionic current is blocked. This current blockage is used to detect the residence time of DNA bases in the pore [67]. (b) Chain translocation through a nanopore. The instantaneous translocation coordinate is s(t) and the bead velocity in the pore is v(t). The driving force is due to a chemical potential gradient within the pore, f = (ni — Adapted from [68]. Reproduced... 

Figure 8.10 A typical ionic current trace, from computer simulations, as a polymer molecule undergoes translocation through the aHL protein pore. (From Muthukumar, M. and Kong, C.Y., Proc. Natl. Acad. Sci. USA, 103, 5273, 2006. With permission.)...

The ability of certain polymer sequences to spontaneously form secondary structures influences their migration through nanopores. As examples, let us consider the translocation events of single-stranded polynucleotides through a-hemolysin protein pore in the electrophysiology experiments. The event plots of translocation (every data point in the plot referring to the dwell time and the ionic current of a particular blockade event) for polycytidylic acid (poly C) and polydeoxycytidylic acid (poly dC) are compared in Figure 11.3a,... 

The Bcl-2 family of oncoproteins is known to play an important role in apoptosis through their ability to regulate cytochrome c release from mitochondria [11,15]. The antiapoptotic proteins Bcl-2 and Bc1-Xl prevent cytochrome c release, whereas the proapoptotic family members (e.g.. Bad, Bid, Bik, Bax) facilitate cytochrome c efflux or block the protective effects of Bcl-2 and Bc1-Xl. The mechanism involved is unclear the Bcl-2 family proteins may interact directly with the MTP (mitochondrial permeability transition) protein complex (the PTPC) or form independent ionic pores in the outer mitochondrial membrane (Fig. 3). Nonetheless, cytochrome c-depen-dent caspase-3 activation and changes in the expression or phosphorylation state of Bcl-2 family proteins are taken as indicative of mitochondria-dependent apoptotic pathways. It is important to remember that other apoptogenic proteins are also present in the mitochondrial intermembrane space, including smac/ DIABLO and flavoprotein (AIF) [10,11,60]. The release stimuli for the latter factors, which are currently being elucidated, may also involve the permeability transition or the Bcl-2 family proteins [37]. 

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