Calcium-activated potassium

Vergara, C, Latorre, R, Marrion, NV and Adelman, JP (1998) Calcium-activated potassium channels. Curr. Op. Neurobiol. 8 321-329. 

The characteristics of the four major classes of histamine receptors are summarized. Question marks indicate suggestions from the literature that have not been confirmed. AA, arachidonic acid DAG, diacylglycerol Iko,2+, calcium-activated potassium current IP3, inositol 1,4,5-trisphosphate NHE, sodium-proton exchange, PKC, protein kinase C NO, nitric oxide PTPLC, phosphoinositide-specific phospholipase C TXA2, thromboxane A2. Has brain-penetrating characteristics after systemic administration. 

Patterson AJ, Henrie-Olson J, Brenner R (2002) Vasoregulation at the molecular level a role for the betal subunit of the calcium-activated potassium (BK) channel. Trends Cardiovascul Med 12(2) 78-82... 

Brenner R, Perez GJ, Bonev AD et al 2000 Vasoregulation by the fi 1 subunit of the calcium-activated potassium channel. Nature 407 870-876... 

VanderMaelen, C. P., and Aghajanian, G. K. (1983) Evidence for a calcium-activated potassium conductance in serotonergic dorsal raphe neurons. Neurosci. Abstr., 9 500. 

FIGURE 2 Examples of the variety of structures obtained in natural product screens. I, zaragozic acid A, is an inhibitor of mammalian and fungal sterol synthesis, obtained from fungi (48) II, L-696,474, is an inhibitor of the HIV protease, obtained from fungi (51) III, dehydrosoyasaponin I, is an agonist of the calcium-activated potassium channel, obtained from a medicinal plant (58) IV, tetrandrine, is an inhibitor of L-type calcium channels, obtained from a plant (78). 

Xu M et ai, Shearinines D-K, new indole triterpenoids from an endophytic Penicillium sp. (strain HKI0459) with blocking activity on large-conductance calcium-activated potassium channels, Tetrahedron 63 435—444, 2007. 

Boettger, M. K., Till, S., Chen, M. X., Anand, U., Otto, W. R., Plumpton, C., Trezise, D. J., Tate, S. N., Bountra, C., Coward, K., Birch, R., Anand, P. Calcium-activated potassium channel SK1-and IK1-like immunoreactivity in injured human sensory neurones and its regulation by neurotrophic factors, Brain 2002, 125, 252-260. 

Torres GE, Chaput Y, Andrade R. Cyclic AMP and protein kinase A mediate 5-hydroxytryptamine type 4 receptor regulation of calcium-activated potassium current in adult hippocampal neurons. Mol Pharmacol 1995 47 191-197. 

Regulation of Calcium-Activated Potassium Currents by 5-HT4 and 5-HT7 Receptors in the Hippocampus... 

Many neurons in the central and peripheral nervous system display pronounced calcium-dependent afterhyperpolarizations (AHP) that play a key role in sculpturing neuronal responses to excitatory stimuli (3). These AHPs are mechanistically complex and are mediated by the activation of at least three types of calcium-activated potassium current (3,4). One of the classical effects signaled via cAMP and PKA in the central nervous system is the inhibition of the current responsible for the slow component of the AHP (sAHP). Because the sAHP curtails sustained spiking in response to excitatory stimuli, the net effect of inhibiting the current underlying this afterpotential is to increase neuronal excitability (5) (Fig. 1A). 

Combined, the above-outlined results indicate that both 5-HT4 and 5-HT7 receptors can regulate membrane excitability in the central nervous system (CNS) by targeting the calcium-activated potassium channels mediating /sAHP, the... 

Sah P, Faber ES. Channels underlying neuronal calcium-activated potassium currents. Prog Neurobiol 2002 66 345-353. 

Faber ES, Sah P. Calcium-activated potassium channels multiple contributions to neuronal function. Neuroscientist 2003 9 181-194. 

Andersson, D. A., Zygmunt, P. M., Movahed, P., Andersson, T. L., and Hogestatt, E. D. 2000. Effects of inhibitors of small- and intermediate-conductance calcium-activated potassium channels, inwardly-rectifying potassium channels and Na(+)/K(+) ATPase on EDHF relaxations in the rat hepatic artery. Br. J. Pharmacol. 129 1490-1496. 

Joiner, W. J., Wang, L.-Y., Tang, M. D., and Kaczmarek, L. K. 1997. hSK4, a member of a novel subfamily of calcium-activated potassium channel. Proc. Natl. Acad. Sci. USA 94 11013-11018. 

Kohler, M., Hirschberg, B., Bond, C. T., Kinzie, J. M., Manion, N. V., Maylie, J., and Adelman, J. P. 1996. Small-conductance,calcium-activated potassium channels from mammalian brain. Science 273 1709-1714. 

Marchenko, S. M., and Sage, S. O. 1996. Calcium-activated potassium channels in the endothelium of intact rat aorta. J. Physiol. (London) 492 53-60. 

Pena, T. L., and Rane, S. G. 1997. The small conductance calcium-activated potassium channel regulates ion channel expression in C3H10T1/2 cell ectopically expressing the muscle regulatory factor MRF4. J. Cell. Biochem. 272 21909-21916. 

Wulff, H., Gutman, G. A., Cahalan, M. D., and Chandy, K. G. 2001. Delineation of the clotrimazole/TRAM-34 binding site on the intermediate conductance calcium-activated potassium channel, IKCal. J. Biol. Chem. 276 32040-32045. 

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. 

Wulff H et al (2007) Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications. Curr Med Chem 14 1437-1457... 

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