7oxf

Structural highlights

Function

APAM_APIME Neurotoxin that blocks the small-conductance calcium-activated potassium (SK) channels KCa2.1/KCNN1/SK1, KCa2.2/KCNN2/SK2 and KCa2.3/KCNN3/SK3 (PubMed:6122211, PubMed:9459560, PubMed:9287325, PubMed:10696100, PubMed:11533126, PubMed:11212219, PubMed:17142458, PubMed:20562108, PubMed:32560481). Also irreversibly blocks the voltage-gated potassium channel Kv1.3/KCNA3 (IC(50)=13 nM) (PubMed:28108814). Potently blocks human, rat and mouse KCa2.2/KCNN2/SK2 channels (IC(50)=27-140 pM), and moderately blocks human and rat KCa2.3/KCNN3/SK3 channels (IC(50)=0.6-4 nM), and human (IC(50)=0.7-12 nM) and mouse (IC(50)=28 nM) KCa2.1/KCNN1/SK1 channels (PubMed:9459560, PubMed:9287325, PubMed:10696100, PubMed:11533126, PubMed:11212219, PubMed:17142458, PubMed:20562108). However, other reports found that it did not block the human KCa2.1/KCNN1/SK1 channels (PubMed:9287325). Also able to inhibit neuromuscular transmission by a mechanism independent of the blockade of SK channels, which may involve the activation of inhibitory muscarinic M2 receptors on motor nerve terminals (PubMed:19818752).^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]}

References

1. ↑ Strobaek D, Jorgensen TD, Christophersen P, Ahring PK, Olesen SP. Pharmacological characterization of small-conductance Ca(2+)-activated K(+) channels stably expressed in HEK 293 cells. Br J Pharmacol. 2000 Mar;129(5):991-9. doi: 10.1038/sj.bjp.0703120. PMID:10696100 doi:http://dx.doi.org/10.1038/sj.bjp.0703120
2. ↑ Grunnet M, Jensen BS, Olesen SP, Klaerke DA. Apamin interacts with all subtypes of cloned small-conductance Ca2+-activated K+ channels. Pflugers Arch. 2001 Jan;441(4):544-50. doi: 10.1007/s004240000447. PMID:11212219 doi:http://dx.doi.org/10.1007/s004240000447
3. ↑ Hosseini R, Benton DC, Dunn PM, Jenkinson DH, Moss GW. SK3 is an important component of K(+) channels mediating the afterhyperpolarization in cultured rat SCG neurones. J Physiol. 2001 Sep 1;535(Pt 2):323-34. doi: 10.1111/j.1469-7793.2001.00323.x. PMID:11533126 doi:http://dx.doi.org/10.1111/j.1469-7793.2001.00323.x
4. ↑ Nolting A, Ferraro T, D'hoedt D, Stocker M. An amino acid outside the pore region influences apamin sensitivity in small conductance Ca2+-activated K+ channels. J Biol Chem. 2007 Feb 9;282(6):3478-86. doi: 10.1074/jbc.M607213200. Epub 2006, Dec 1. PMID:17142458 doi:http://dx.doi.org/10.1074/jbc.M607213200
5. ↑ de Matos Silva LF, de Paula Ramos ER, Ambiel CR, Correia-de-Sa P, Alves-Do-Prado W. Apamin reduces neuromuscular transmission by activating inhibitory muscarinic M(2) receptors on motor nerve terminals. Eur J Pharmacol. 2010 Jan 25;626(2-3):239-43. doi: 10.1016/j.ejphar.2009.09.064. , Epub 2009 Oct 8. PMID:19818752 doi:http://dx.doi.org/10.1016/j.ejphar.2009.09.064
6. ↑ Lamy C, Goodchild SJ, Weatherall KL, Jane DE, Liegeois JF, Seutin V, Marrion NV. Allosteric block of KCa2 channels by apamin. J Biol Chem. 2010 Aug 27;285(35):27067-27077. doi: 10.1074/jbc.M110.110072. Epub , 2010 Jun 18. PMID:20562108 doi:http://dx.doi.org/10.1074/jbc.M110.110072
7. ↑ Voos P, Yazar M, Lautenschlager R, Rauh O, Moroni A, Thiel G. The small neurotoxin apamin blocks not only small conductance Ca(2+) activated K(+) channels (SK type) but also the voltage dependent Kv1.3 channel. Eur Biophys J. 2017 Sep;46(6):517-523. doi: 10.1007/s00249-016-1196-0. Epub 2017 , Jan 20. PMID:28108814 doi:http://dx.doi.org/10.1007/s00249-016-1196-0
8. ↑ Park J, Jang KM, Park KK. Apamin Suppresses LPS-Induced Neuroinflammatory Responses by Regulating SK Channels and TLR4-Mediated Signaling Pathways. Int J Mol Sci. 2020 Jun 17;21(12). pii: ijms21124319. doi: 10.3390/ijms21124319. PMID:32560481 doi:http://dx.doi.org/10.3390/ijms21124319
9. ↑ Hugues M, Romey G, Duval D, Vincent JP, Lazdunski M. Apamin as a selective blocker of the calcium-dependent potassium channel in neuroblastoma cells: voltage-clamp and biochemical characterization of the toxin receptor. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1308-12. doi: 10.1073/pnas.79.4.1308. PMID:6122211 doi:http://dx.doi.org/10.1073/pnas.79.4.1308
10. ↑ Ishii TM, Maylie J, Adelman JP. Determinants of apamin and d-tubocurarine block in SK potassium channels. J Biol Chem. 1997 Sep 12;272(37):23195-200. doi: 10.1074/jbc.272.37.23195. PMID:9287325 doi:http://dx.doi.org/10.1074/jbc.272.37.23195
11. ↑ Mourre C, Fournier C, Soumireu-Mourat B. Apamin, a blocker of the calcium-activated potassium channel, induces neurodegeneration of Purkinje cells exclusively. Brain Res. 1997 Dec 19;778(2):405-8. doi: 10.1016/s0006-8993(97)01165-7. PMID:9459560 doi:http://dx.doi.org/10.1016/s0006-8993(97)01165-7