Molecular struture of ion channels_1

The detailed arrangement of the pore and the way the

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Unformatted text preview: ir legs and wings when exposed to ether. This turns out to be due to mutations in specific genes. Among these strains of 8 mutant flies are some that have defects in a particular gene, a piece of DNA that has been termed the Shaker locus (because these flies shake when anesthetized). The defect (shaking) was due to the loss of a particular K+ channel (as we shall see below, there are hundreds of different types of K+ channels). Recall, that the function of K+ channels is to repolarize action potentials and thereby shorten their durations. The loss of this K+ channel caused abnormally long action potentials in some, but not all, axons of Shaker flies (but only when they were anesthetized). When the prolonged action potentials arrived at muscle fibers, they cause unusually prolonged transmitter release, prolonged muscular contractions and hence shaking. When the sequence of the Shaker K+ channel was determined, protein encoded by the gene was termed the subunit. The subunit is in some ways strikingly similar to the Na+ channels described previously, and in other ways is strikingly different. The features that are similar are that the subunit has six membrane spanning regions, S1S6, with one S4 region that closely resembled the S4 voltage sensor in the Na+ channel. What is different is that the subunit is the size of the Na+ channel but with a structure similar to one domain of a Na+ channel. Recall that all 4 domains of the Na+ channel are produced by a single gene. In contrast, genes that code for K+ channels only transcribe mRNA that produce one subunit. An individual subunit cannot by itself form a channel. Rather, the Shaker K+ channel is formed by combining four subunits into a tetramer. Indeed, it is now known that all K+ channels are formed from four subunits, where each subunit is encoded by one gene. In short, the K+ channel, like the Na+ channel, has four domains, with each domain composed of six transmembrane segments, S16. However, unlike Na+ channels where the entire channel is encoded by one gene, only one domain (subunit) of the K+ channel is produced by single gene. The entire K+ channel is composed of four separate subunits that combine to resemble the Na+ channel (Fig. 9). Like the Na+ channel, each subunit has 6 transmembrane segments, where the S4 segment is the voltage sensor, as in Na channels. Figure 8. Comparison of subunit composition in Na+ compared to K+ channels. 9 Figure 9. Top view showing how subunits tetramerize to form a functional K+ channel. The 4 subunits that compose the channel correspond to the four domains in Na+ channels. Potassium channel diversity There are a huge variety of voltage gated K+ channels, far more than Na+ channels and far more than were ever suspected. Each type has its unique features. Some potassium channels, such as the Shaker K+ channel, have fast activation and have inactivation gates, similar to those on Na+ channels. Other K+ channels are slower (activate slower) and do not have inactivation gates. The K+ channel that we discussed in previous chapters that acts to shape the action potential in the squid giant axon, as one example, does not have an inactivation gate and is slower than the Shaker K+ channel. Some of the diversity is a consequence of different genes that encode different K+ channels. The K+ channels in the squid axon, for example, are produced by a different gene than the Shaker K+ channel. But there are also two other factors that account for K+ channel diversity. One factor is that there is substantial alternative splicing of the RNAs transcribed by potassium channel genes. The DNA of all genes contain expressed sequences called exons, which code for the protein, and noncoding sequences called introns. Because RNA is synthesized from this DNA, the RNA, called premRNA, also contains the exons as well as noncoding introns. During the production of the mature mRNA that encodes the protein, the introns are cut out and the exons are spliced together to produce a competent mRNA that is translated in the cytoplasm. If the splicing results in the incorporation of dif...
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This note was uploaded on 09/17/2009 for the course BIO 365R taught by Professor Draper during the Spring '08 term at University of Texas at Austin.

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