K+ channels genes

Fig. 4. Schematic organization of the Shaker K channel gene. The coordinates of the physical map are as in [9]. The direction of transcription is indicated by arrows. Approximate location of exons is given by boxes. Open box corresponds to noncoding exons, lettered boxes to alternative amino-terminal ends of Shaker channel proteins and the core region, respectively, numbered boxes to the two alternative carboxy-terminal ends. Exon numbers are as in [53].

Keywords Biomarker Cancer cells K+ channels Gene therapy Oncogenesis... 

The potassium channels are highly heterogeneous. The K channels gene only encodes a single repeat and four polypeptides come together to form the channel. Four types can be distinguished (1) the voltage-dependent K channels (2) the Ca" -activated channels (3) the receptor-coupled K" " channels, and other K channels (ATP-sensitive K" " channels, Na -activated K" " channels, etc.). 

Myotonia is muscle stiffness, in which muscle relaxation after voluntary contraction is impaired. Mutations in several ion channel genes (Cl, Na, Ca, K channels) can cause myotonias, which can sometimes be differentiated clinically (e.g. paramyotonia is cold-sensitive). C1C-1 mutations cause pure myotonia congenita which is not sensitive to temperature. Channel myotonia comes in a recessive (Becker type)... 

About 78 human genes encoding a variety of K+ channels and auxiliary subunits have been identified (Fig. 1 Table 1). While the K+ channels are diverse, they share with a unique conducting pore highly selective for K+ ions. TheK+ channels ar e tetramers composed of four a subunits that form the conducting pore. On the basis of primary amino acid sequence of a subunit, K+ channels can be classified into three major families (Fig. 2). 

This family of K+ channels, with >50 distinct gene members, typically contains four putative transmembrane and two pore domains. The G(Y/F)G motif is... 

Potassium Channels. Table 1 Human K+ channel auxiliary subunits genes, localization, function, and disorders... 

Voltage-gated K Channels. Table 2 Kv-channel genes associated with heritable diseases... 

Kang J, Chen XL, Wang H, et al Interactions of the narcotic 1-alpha-acetylmethadol with human cardiac K+ channels. Eur J Pharmacol 458 25-29, 2003 Katchman AN, McGroary KA, Kilborn MJ, et al Influence of opioid agonists on cardiac human ether-a-go-go-related gene K(+) currents. J Pharmacol Exp Ther 303 688-694, 2002... 

Historically the Shaker (Sh) K channel was the first K channel which was cloned and characterized [6-10]. Subsequently many more channel cDNAs and genes have been isolated and studied. Yet Sh channels remained in the forefront of channel research. The study of Sh channel mutants has provided the most thorough insight into structure-function relationships of K channels to date. I will first discuss in this chapter the primary sequences of voltage-gated channels. I will only use a few selected examples for discussion. As of this time, so many related K channel protein sequences have been published that it is not feasible to discuss all of them. Subsequently, I will describe in detail the present knowledge about functional K" " channel domains which are implicated in activation, inactivation and selectivity of the channel. 

The H2 receptor is the second class of HA receptors. This is another G-protein-coupled receptor but, unlike the Hi receptor, the H2 receptor is coupled to adenylyl cyclase via the GTP-binding Gs protein (Hill et ah, 1997). Encoded by an intronless gene and located on human chromosome 5, the H2 receptor is made up of c. 358 amino acids (Gantz et ah, 1991 Traiffort et ah, 1995). Activation of the H2 receptor causes an accumulation of cAMP and activation of protein kinase A that eventually leads to the activation of cyclic-AMP-response element (CRE)-binding protein (CREB) (Hill et ah, 1997). In neurons, the H2 receptor mediates its excitatory effects by blocking the Ca2+-dependent K+ channel (Haas Konnerth, 1983). 

The ability of morphine to desensitize other neurotransmitter receptors coupled to K+ channels may cause long-term consequences in the activity of neurons. The uncoupling of K+ channel from non-opioid receptors that normally tonically inhibit cell firing could result in an increase in the basal firing of the cells. Changes in the set point of neuronal firing could influence gene expression in the cells and alter the molecular properties of the neurons. 

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