Ionic channel, concept

We recently proposed a completely electronic model for the excitability of nerve membranes that is based on the assumption of electron-donating, electron-accepting, and electron-storing properties of macromolecules or of protein-lipid complexes which constitute the ionic channels of the nerve membrane (63). This model, which is based on simple physical concepts with easily defined parameters, reproduces the empirical Hodkgin-Huxley equations rather well and also explains how different types of drugs may work on nerves. The model is easily extended to other excitable complexes like the receptor protein complex at nerve synapses and the rodopsin molecules in the retina. Nor is it inconceivable to build a model for the function of smell that is based on electronic triggering of ionic channels which are affected by molecules adsorbed onto or dis-... 

The development of the concept of ionic channel started with the realisation by Bernstein that cellular excitability was a property of the membrane. The starting point at the experimental level was the observation by Cole and Curtis that, concomitant with a propagated electrical impulse (manifestation of cellular electrical excitability) in the squid giant nerve fibre, a decrease in the electrical resistance took place with no detectable change in the membrane capacitance. This result lent strong support to Bernstein s concept and clearly indicated that the most plastic components of the axolemma, the proteins, underwent structural transitions leading to a transient increase in ionic fluxes. 

For biological membranes and polymer-resin membranes, which may contain charged groups within the membrane matrix, the above argument with regard to the contribution of the surface potential to the transmembrane potential may not be valid. In particular, when there are highly conductive ionic channels composed of lipoprotein molecular assemblies within the membrane (where channels may be mostly hydrophilic and probably main ionic transport pathways across the membranes), the observed transmembrane potential is a very complicated mixture of ion diffusion and Donnan equilibrium potentials. The idealized surface potential concept may not be a good approach to analyze such a transmembrane potential. 

The concept of calcium antagonism as a specific mechanism of drug action was pioneered by Albrecht Fleckenstein and his colleagues, who observed that verapamil and subsequently other drugs of this class mimicked in reversible fashion the effects of Ca++ withdrawal on cardiac excitability. These drugs inhibited the Ca" + component of the ionic currents carried in the cardiac action potential. Because of this activity, these drugs are also referred to as slow channel blockers, calcium channel antagonists, and calcium entry blockers. 

Studies on artificial ion channels are expected to provide important information on molecular mechanisms and to deepen our understanding of natural ion channels through the establishment of a detailed structure-function relationship. At the same time, the research will contribute to the fascinating area of nanoscale transducers, and may eventually lead to the development of so-called molecular ionics. Here, the author would like to describe the basic concept for the molecular design of various artificial ion channels and to compare their characteristics in the hope of stimulating a future explosion of this research field. Special attention is focused on non-peptidic approaches. Helical bundle approaches " and studies on modified antibiotics " are beyond the scope of this review. 

Both the inhaled and the intravenous anesthetics can depress spontaneous and evoked activity of neurons in many regions of the brain. Older concepts of the mechanism of anesthesia evoked nonspecific interactions of these agents with the lipid matrix of the nerve membrane (the so-called Meyer-Overton principle)—interactions that were thought to lead to secondary changes in ion flux. More recently, evidence has accumulated suggesting that the modification of ion currents by anesthetics results from more direct interactions with specific nerve membrane components. The ionic mechanisms involved for different anesthetics may vary, but at clinically relevant concentrations they appear to involve interactions with members of the ligand-gated ion channel family. 

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