Calcium-dependent potassium channel

ICA -17043 is a novel inhibitor of the Gardos channel (a calcium-dependent potassium channel). This drug is indicated for the treatment of a hematologic genetic disease (sickle cell disease) (Phase 11) (Figure 8.88). 

Brodie MS et al Ethanol interactions with calcium-dependent potassium channels. Alcohol Clin Exp Res 2007 31 1625. [PMID 17850640]... 

Gerlach, A. C., Gangopadhyay, N. N., and Devor, D. C. 2000. Kinase-dependent regulation of the intermediate conductance, calcium-dependent potassium channel, hIKl. J. Biol. Chem. 275 585-598. 

Heme oxygenase-2 is an oxygen sensor for a calcium dependent potassium channel [44]. Knock-down of heme oxygenase-2 activity was re-instated by CO. 

Brayden, J. E., Nelson, M. T. (1992). Regulation of arterial tone by actiA tion of calcium-dependent potassium channels. Science, 25d(5056), 532-535. 

Chlorzoxazone appears to increase the activity of calcium-dependent potassium channels, resulting in hypopolarization of spinal and supraspinal neurons. This results in a decrease in firing of a-motor neurons and a decrease in spasm. 

NO can also activate calcium-dependent potassium channels independently of cGMP (Bolotina et al., 1994). 

Bolotina, V. M., Najibi, S., Palacino, J. J., Pagano, P. J., and Cohen, R. A. (1994). Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature London) 368, 850-883. 

In the inside-out configuration, the internal membrane surface is exposed to the recording chamber bath. In this way it is possible to interact directly with it, by modifying the composition of the solution of the bath. Using this configuration it is possible to study the properties of channels that are normally modulated by intracellular substances, as in the case of calcium-dependent potassium channels (see for example ref. [28]). 

Cornfield DN, Reeve HL, Tolarova S, Weir EK, Archer SL. Oxygen causes fetal pulmonary vasodilation through activation of a calcium-dependent potassium channel. Proc Natl Acad Sci USA 1996 93 8089-8094. 

Repaglinide en nateglinide are not sulfonylurea agents but their mechanism of action is very alike. Repaglinide is the first carbamoylmethyl-benzoic acid derivative that has been registred for the treatment of diabetes mellitus. It closes ATP-dependent potassium channels in the beta cell membrane with consequent depolarization, opening of calcium channels and increased insulin release. It is rapidly absorbed with peak plasma levels after 1 hour. It has a protein binding of over 98%. 

While researchers believe that the GABAergic response is responsible for the major effects of the BZs, other mechanisms of action have been proposed. The BZs increase calcium-dependent potassium, inhibit tetrodotoxin-sensitive NA channels, and antagonize cholecystokinin-induced excitation. The clinical relevance of these actions is unknown at this time (Polk, 1988 Hobbs et ah, 1996). 

An inhibition of the voltage-dependent potassium channels located in presy-naptic terminals can be expected to lead to spike broadening, an increase in calcium influx, and facilitation of neurotransmitter release (19). Thus, one potential functional role for 5-HT4 receptors could be the facilitation of synaptic transmission in the CNS. Although evidence for such an effect remains equivocal in CNS neurons, activation of 5-HT4 receptors has been reported to increase synaptic transmission in the myenteric nervous system (20). Such an effect might contribute to the prokinetic activity of benzamide 5-HT4 receptor agonists in the gastrointestinal tract. 

The role of calcium in regulating cardiovascular physiology is presented in the fourth section of this volume. House et al. have provided an excellent review on the structure of calmodulin-dependent protein kinase II and its role in the contractility as well as proliferation and migration of VSMC. Banderali et al. have examined in detail the cellular regulation and pharmacological properties of calcium-activated potassium channels and their role in control of vascular tone by endothelium. 

Nicorandil is an effective vasodilator through two actions. It acts as a nitrate by activating cyclic GMP (see above) but also opens the ATP-dependent potassium channel to allow potassium efflux and h5rperpolarisation of the membrane which reduces calcium ion entry and induces muscular relaxation. It is indicated for use in angina, where it has similar efficacy to p-blockade, nitrates or calcium channel blockade. It is administered orally and is an alternative to nitrates when tolerance to these is a problem, or to the other classes when these are contraindicated by asthma or cardiac failure. Adverse effects to nicorandil are similar to those of nitrates, with headache reported in 35% of patients. It is the only antianginal drug for which at least one trial has demonstrated a beneficial influence upon outcome. ... 

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