K+and Ca+channels

T. Schneidere, P. Igelmund, J. Hescheler (1997). G protein interaction with K and Ca channels. 

Alkaloids that structurally mimic neurotransmitters can bind to neuroreceptors and either activate (agonists) or inactivate (antagonists) them (Table 1.1). Additional important targets are ion channels, such as the Na" ", K, and Ca + channels several alkaloids are known that inhibit or activate these ion channels (Table 1.1). 

Na channel P subunits, the Drosophila Na channel auxiliary subunit TipE, and the P subunits of voltage-gated K and Ca channels have similar functions in terms of modulation of channel activity (Adelman 1995, Isom et al 1994, Warmke et al 1997). As will be discussed below, however, only the mammalian Na channel P subunits also function as cell adhesion molecules (CAMs). What other proteins associate with Na channels and contribute to the ion conduction proteome in excitable cells How is Na channel function affected by these associated proteins and by the local cellular environment Recent advances, outlined below, have begun to answer these important questions in channel biology. 

G-proteins can also control potassium (K ) and Ca channel function thus regulating membrane excitability and transmitter release, e.g. 5-HTia receptor activation inhibits adenylate cyclase and increases conductance (hyperpolarisation). 

Clidinium bromide, another quaternary ammonium compound with antimuscarinic activity, is used in a fixed combination with chlordiazepoxide hydrochloride (2.5 mg of clidinium and 5 mg of chlordiazepoxide Librax) however, such combinations are of limited value in patients with IBS because of the risk of habituation and rebound withdrawal. Cimetropium is another antimuscarinic compound that reportedly is effective in patients with IBS. Otilonium bromide has been used extensively for patients with IBS in other parts of the world. It is an ammonium salt with antimuscarinic effects that also appears to block Ca + channels and neurokinin NK-2 receptors. Mebeverine hydrochloride is a derivative of hydroxybenzamide that appears to have a direct effect on the smooth-muscle cell, blocking K+ and Ca channels. It is widely used outside of the United States as an antispasmodic agent for patients with IBS. 

The existence of voltage-gated ion channels in bilayers are not limited to nerve membranes. They are present to some extent in all cell membranes. Even the paramecium has at least seven kinds of Na, K, and Ca channels.4 Channels may also be formed by many peptide antibiotics. Among them are the human defensins (Chapter 31) and the 20-residue alamethi-cin. Six to eleven of the mostly helical monomers of that antibiotic assemble to form a single voltage-dependent channel.4 4 484a jj g bacterial toxin colicin El (Box 8-D) forms voltage-dependent channels within bacterial membranes. ... 

Opioid receptors. Direct binding of highly radioactive opiates has permitted localization of specific opiate receptors of several types. The three major types (p, 5, k) are all 7-helix receptors coupled to adenylate cyclase, K+ and Ca + channels, and the MAP kinase cascade. The p receptors bind morphine most tightly. These receptors are found in various cortical and subcortical regions of the brain. Most narcotics are polycyclic in nature and share the grouping indicated in Fig. 30-30. However, the flexible molecule methadone binds to the same receptors. Among antagonists that block the euphoric effects of opiates the most effective is naloxone (Fig. 30-30). 

Proarrhythmia potential hERG activity (automated patch clamp) and assessment of potential for multicardiac ion channel blockade (e.g., evidence of Na, K, and Ca channel binding). 

Ganfomina A, Lopez-Bameo J. Potassium channel types in arterial chemoreceptor cells and their selective modulation by oxygen. J Gen Physiol 1992 100 401-426. Lopez-Bameo J, Pardal R, Montoro RJ, Smani T, Garcia-Hirschfeld J, Urena J. K and Ca channel activity and cytosolic [Ca +] in oxygen-sensing tissues. Respir Physiol 1999 115 215-227. 

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