Na+and K+channels

During excitation, ion channels open and close and a few ions flow 98 Gating mechanisms for Na+ and K+ channels in the axolemma are voltage-dependent 98... 

FIGURE 6-3 Simplified kinetic model for opening and closing steps of Na+ and K+ channels. (Adapted from Hodgkin and Huxley [6].)... 

Fig. 16.8. Model of inactivation of voltage-gated Na and K channels, a) Inactivation of the Na channel. On inactivation of the Na channel, the loop, which binds domain III and domain IV of the a-subunit, positions itself in the cytoplasmic entrance of the pore and closes it. The indicated hydrophobic amino acids of the connecting loop are involved in the inactivation, b) Inactivation of the K channel. The model assumes that a compact structural part of the C terminus of the P subunit is aligned in the pore and transiently closes it. The inactivating structural part is linked to the pore via a flexible structural element and contains a functionally important leucine residue and a lot of positive charges. According to CatteraU, (1995).

I disagree with Dr. Thomas that there are no known biological channels or carriers. I know of at least one example of a clearly demonstrated channel. This is the acetylcholine activated channel in denervated muscle demonstrated so elegantly by Neher and Sackmann (Nature, 260, 119, 1976), who resolved unit conductance jumps that are far too large to be accounted for by a carrier mechanism. A less unambiguously demonstrated example of channels are the Na+ and K+ channels of nerve, which both by noise analysis and pharmacological evidence imply the movement of about 1000 times as many ions in a unit of time as is reasonable for any diffusive carrier mechanism across the entire membrane. 

Professor Eisenman, there is a large body of results indicating the existence of channel systems. One could mention the Ca2+ ATPase of sarcoplasmic reticulum, the FF transporting ATPase of the inner mitochondrial membrane, the purple protein system of halobacteria, the Na and K+ channels of the axonal membranes. Apart from the classical type of evidence provided, for example, by the noise fluctuation technique, we now even begin to see direct electron microscopic evidence for the existence of transport-related openings in biological membranes. On the other hand, solid evidence for the existence of mobile carriers in eucaryotic cell membranes is very scarce, if not outright absent. 

The voltage-gated Na+ and K+ channels of neuronal membranes carry the action potential along the axon as a wave of depolarization (Na+ influx) followed by repolarization (K+ efflux). 

The axon is effectively insulated from the surrounding medium by the myelin sheets except for special regions, the nodes of Ranvier, which lie at 1-to 2-mm intervals along the nerve. The nerve impulse in effect jumps from one nerve to the next. This saltatory conduction occurs much more rapidly (up to 100 m / s) than conduction in unmyelinated axons. It depends upon Na+ and K+ channels that are concentrated in the nodes of Ranvier. 

External Ca2+ entry, leading to the increase of [Ca2+] , has been reported to occur after electrical (MacVicar el al., 1991) or chemical (Jensen and Chiu, 1991) depolarization of cultured astrocytes, as well as after KC1 depolarization of astrocytes in situ utilizing acute brain slices (Porter and McCarthy, 1995). Accordingly, astrocytes express membrane ion channels, including voltage-sensitive Na+ and K+ channels as well as VSCCs, which may represent the molecular substrate of this aptitude (Barres et al., 1990 Verkhratsky and Steinhauser, 2000). 

Ionotropic ATP receptors ATP is an excitatory NT in the central nervous system (CNS) and the peripheral nervous system (PNS). ATP acts via ionotropic, oligomeric P2X receptors that form ATP-gated Na+ and K+ channels which also have a significant permeability for Ca2+. ATP also acts via excitatory, metabotropic, G protein-linked P2Y receptors (see Chapter 5). 

How do ion chaimels, vital to a wide array of biological functions, operate at a molecular level We will examine three chaimels important in the propagation of nerve impulses the ligand-gated channel the acetylcholine receptor channel, which communicates the nerve impulse between certain neurons and the voltage-gated Na+ and K+ channels, which conduct the nerve impulse down the axon of a neuron. 

Ion channels allow the rapid movement of ions across the hydrophobic barrier of the membrane. Such channels allow ions to flow down their concentration gradients. The channels have several features in common (1) ion specificity, (2) the existence of open and closed states, (3) regulation by ligands or voltage. Ion channels are exemplified by the Na+ and K+ channels responsible for nerve impulses. 

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