Potassium channels for

The mu, delta and kappa opioid receptors are coupled to G° and G proteins and the inhibitory actions of the opioids occur from the closing of calcium channels (in the case of the K receptor) and the opening of potassium channels (for /i, d and ORL-1). These actions result in either reductions in transmitter release or depression of neuronal excitability depending on the pre- or postsynaptic location of the receptors. Excitatory effects can also occur via indirect mechanisms such as disinhibition, which have been reported in the substantia gelatinosa and the hippocampus. Flere, the activation of opioid receptors on GABA neurons results in removal of GABA-mediated inhibition and so leads to facilitation. 

Figure 7.8 Simulated action potential from the Flodgkin-Huxley model. The upper panel plots action potential for three different values of applied current. The lower panel plots the predicted conductances of the sodium and potassium channels for the case of Iapp = 6.2 qA-cm-2, for which sustained period firing of the nerve cell is predicted.

Another group of three-disulfide conotoxins can be found within the A-superfamily. The aA- and kA-conotoxins contain three disulfide bonds with three loops but different disulfide pairing and loop sizes. They also have different molecular targeting nAChR for the aA-conotoxins versus potassium channels for the kA-conotoxins. ... 

Absorption, Transportation, and Distribution Rubidium is very well absorbed from the alimentary tract of animals (Schafer and Forth 1983), with absorption in humans exceeding 60% in both sexes (Table 1.4-5). Rubidium resembles potassium in its pattern of absorption (channels). On the basis of studies with brush border membrane vesicles isolated from the jejuna of rabbits, potassium and rubidium apparently share a transport system. All plant and animal cells are apparently permeable to rubidium ions at rates comparable with those of potassium (Nielsen 1986). It seems that rubidium uses the potassium channels for entering the cell (Clay and Shlesinger 1983, Gallacher et al. 1984). All soft tissues of the body have rubidium concentrations that are high compared with trace elements, with a typical... 

Walsh KB (Feb 2015). Targeting cardiac potassium channels for state-of-the-art drug discovery. Expert Opin Drug Discov 10(2) 157-169. 

There ate many classes of anticonvulsant agent in use, many associated with side effect HabiUties of unknown etiology. Despite many years of clinical use, the mechanism of action of many anticonvulsant dmgs, with the exception of the BZs, remains unclear and may reflect multiple effects on different systems, the summation of which results in the anticonvulsant activity. The pharmacophore stmctures involved are diverse and as of this writing there is htde evidence for a common mechanism of action. Some consensus is evolving, however, in regard to effects on sodium and potassium channels (16) to reduce CNS excitation owing to convulsive episodes. 

The anainoacridines, tacrine (19) and its 1-hydroxy metaboUte, velnacrine (20), are reversible inhibitors of AChE. Tacrine was synthesi2ed in the 1940s and has been used clinically for the treatment of myasthenia gravis and tardive dyskinesia (115). Placebo-controUed studies have indicated modest efficacy of tacrine to treat AD dementia (122,123) and in 1993 the dmg was recommended for approval by the PDA under the trade name Cognex. Tacrine (19) has been shown to interact with sites other than AChE, such as potassium channels (124) and muscarinic receptors. However, these interactions are comparatively weak and are not thought to contribute to the biological activity of the dmg at therapeutic levels (115). 

An alternative approach to stimulate cholinergic function is to enhance the release of acetylcholine (ACh). Compounds such as the aminopyridines increase the release of neurotransmitters (148). The mechanism by which these compounds modulate the release of acetylcholine is likely the blockade of potassium channels. However, these agents increase both basal (release in the absence of a stimulus) and stimulus-evoked release (148). 4-Aminopyridine [504-24-5] was evaluated in a pilot study for its effects in AD and found to be mildly effective (149). 

Opiates iateract with three principal classes of opioid GPCRs )J.-selective for the endorphiQS,5-selective for enkephalins, and K-selective for dynorphias (51). AU. three receptors have been cloned. Each inhibits adenylate cyclase, can activate potassium channels, and inhibit A/-type calcium channels. The classical opiates, morphine and its antagonists naloxone (144) and naltrexone (145), have moderate selectivity for the. -receptor. Pharmacological evidence suggests that there are two subtypes of the. -receptor and three subtypes each of the 5- and K-receptor. An s-opiate receptor may also exist. 

Cromakalim (137) is a potassium channel activator commonly used as an antihypertensive agent (107). The rationale for the design of cromakalim is based on P-blockers such as propranolol (115) and atenolol (123). Conformational restriction of the propanolamine side chain as observed in the cromakalim chroman nucleus provides compounds with desired antihypertensive activity free of the side effects commonly associated with P-blockers. Enantiomerically pure cromakalim is produced by resolution of the diastereomeric (T)-a-meth5lben2ylcarbamate derivatives. X-ray crystallographic analysis of this diastereomer provides the absolute stereochemistry of cromakalim. Biological activity resides primarily in the (—)-(33, 4R)-enantiomer [94535-50-9] (137) (108). In spontaneously hypertensive rats, the (—)-(33, 4R)-enantiomer, at dosages of 0.3 mg/kg, lowers the systoHc pressure 47%, whereas the (+)-(3R,43)-enantiomer only decreases the systoHc pressure by 14% at a dose of 3.0 mg/kg. 

Pinacidil. Piaacidil is a poteat vasodilator, actiag through potassium channel opening effects (242,251—253). Its antihyperteasive effect is greater than that of hydrala2iae and pra2osia ia chronic treatmeat. Its fast oaset of actioa also makes it suitable for use ia hyperteasive crisis. 

Dihydropyridine Z0947 (108) has been identified as a potassium channel opener for use in urinary urge incontinence and an asymmetric synthesis was required for long-... 

Katp channels are the targets for two classes of therapeutic agents, hypoglycaemic drugs like glibencla-mide or nateglinide and potassium channel openers like... 

CFTR has a single-channel conductance of about 8 pS. It is present in the apical membranes of many epithelia. Its mutation leads to the potentially lethal disease cystic fibrosis. In addition to acting as a chloride channel, CFTR is also thought to regulate, e.g., the epithelial sodium channel ENaC, a molecularly unknown outwardly-rectifying chloride channel, and possibly also potassium channels and water channels. Some of these potential regulatory processes, however, are controversial. CFTR also acts as a receptor for bacteria. 

Kv-channel is an abbreviation of voltage-gated potassium channels. K stands for potassium and v for voltage. 

Besides sodium channels, other ion channels such calcium- and potassium channels as well as certain ligand-gated channels are affected by local anaesthetics. However, this plays only a minor role for nerve block but may have more impact on adverse effects induced by systemical concentrations of these drags. 

Brown, DA (2000) The acid test for resting potassium channels. Curr. Biol. 10 R456-R459. Dolphin, AC (1998) Mechanisms of modulation of voltage-dependent calcium channels by G proteins. J. Physiol. 506 3-11. 

This peptide itself has no selectivity for the two CCK receptors, CCK-A and B, which have so far been established to stimulate IP3/DAG while, like substance P, can close potassium channels to increase neuronal activity. The CCK-B receptor is thought to predominate in the CNS but species differences may make this interpretation difficult. It has a wide distribution in the CNS but is also found in the gut whereas the CCK-A receptor is more restricted but is found in the hypothalamus, hippocampus and in the brainstem. There are high levels of the natural peptide, CCK-8 in cortex, hippocampus, hypothalamus, ventral tegmentum, substantia nigra, brainstem and spinal cord. CCK is one of the most abundant peptides in the brain and CCK co-exists with dopamine, substance P, 5-HT and vasopressin. Interestingly, in the dopamine areas, CCK co-exists in the mesolimbic pathways but in the nigrostriatal projections, the peptide and... 

---