Slow channel transport

Substances That Alter Slow Channel Transport... 

Theoretically, substances or interventions that alter slow channel transport may do so in a variety of ways -... 

Many substances inhibit slow channel transport. In addition to the divalent cations already cited (Mn +, Co + and Ni +), protons, La3+, the metabolic inhibitors cyanide and dinitrophenol, are effective inhibitors (24). Other inhibitory agents include acetylcholine, (42) papaverine, (43) pentobarbital, lidoflazine, (44) and adenosine (45) as well as verapamil, nifedipine and diltiazem (1). Precisely how many of these substances interfere with slow channel transport is unknown, although in the case of the metabolic inhibitors we can probably account for their effect in terms of the energy requirements (24) needed for maintaining the configurational state of the cell membrane compatible with the maintenance of normal slow channel ultrastructure. 

Class II could include those drugs which are most effective in blocking slow channel transport in vascular smooth muscle. Nifedipine would provide the prototype for this subgroup (47). 

Class II drugs can be further subdivided into at least three subgroups (Figure 3). For example the effect of diltiazem on the slow channels is more marked in the smooth muscle cells of the coronary (51) than the peripheral vasculature. Nimodipine (52) acts preferentially on slow channel transport in the cerebral vessels, where it blocks thromboxane-induced contractions (53) ... 

In the classification shown in Figure 3 the organic and inorganic inhibitors of slow channel transport have been grouped together as subgroups of a common type of Ca + entry blocker. 

Theoretically it should be possible to classify the slow channel blockers according to whether or not they affect the kinetics of slow channel transport. In this way we could readily separate the nifedipine type of drugs from those that are more like verapamil. Alternatively can these drugs be subgrouped according to their chemistry This possibility seems to be remote. Thus diltiazem is a benzothiazepine derivative (Figure 1 nifedipine is derived from dihydropyridine whilst verapamil has some structural features in common with papaverine. 

Diffusion in liquids is very slow. Turbulent transport or very narrow channels are necessary for good contact between the phases. The droplets must also be very small to minimize transport hmitations within the drops. An estimation of the time constant for diffusion in a 1-mm drop is (f (10-3)2... 

K+ channels selectively transport K+ across membranes, hyperpolarize cells, set membrane potentials and control the duration of action potentials, among a myriad of other functions. They use diverse forms of gating, but they all have very similar ion permeabilities. All K+ channels show a selectivity sequence of K+ Rb+ > Cs+, whereas the transport of the smallest alkali metal ions Na+ and Li+ is very slow—typically the permeability for K+ is at least 104 that of Na+. The determination of the X-ray structure of the K+-ion channel has allowed us to understand how it selectively filters completely dehydrated K+ ions, but not the smaller Na+ ions. Not only does this molecular filter select the ions to be transported, but also the electrostatic repulsion between K+ ions, which pass through this molecular filter in Indian file, provides the force to drive the K+ ions rapidly through the channel at a rate of 107-108 per second. (Reviewed in Doyle et al., 1998 MacKinnon, 2004.)... 

In sum, the natural tendency will be for sodium, calcium, and chloride ions to flow into the neuron and for potassium ions to flow out, and in so doing to reduce the membrane potential to zero. In reality, this is not so easy. The plasma membrane of the neuron is not very permeable to these ions. If it were, it would be impossible to sustain concentration gradients across it. The rate of passive diffusion of these ions across this membrane is very slow, though not zero, and different for each ion. So how do ions get across the neuronal plasma membrane rapidly There are two ways gated channels and active transport by pumps. 

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