Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4
- PMID: 10692449
- DOI: 10.1074/jbc.275.9.6453
Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4
Abstract
We present the cloning and characterization of two novel calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4, that are enriched in the testis and brain, respectively. We compare and contrast the steady state and kinetic properties of these beta subunits with the previously cloned mouse beta1 (mKCNMB1) and the human beta2 subunit (hKCNMB2). Once inactivation is removed, we find that hKCNMB2 has properties similar to mKCNMB1. hKCNMB2 slows Hslo1 channel gating and shifts the current-voltage relationship to more negative potentials. hKCNMB3 and hKCNMB4 have distinct effects on slo currents not observed with mKCNMB1 and hKCNMB2. Although we found that hKCNMB3 does interact with Hslo channels, its effects on Hslo1 channel properties were slight, increasing Hslo1 activation rates. In contrast, hKCNMB4 slows Hslo1 gating kinetics, and modulates the apparent calcium sensitivity of Hslo1. We found that the different effects of the beta subunits on some Hslo1 channel properties are calcium-dependent. mKCNMB1 and hKCNMB2 slow activation at 1 microM but not at 10 microM free calcium concentrations. hKCNMB4 decreases Hslo1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. These results suggest that beta subunits in diverse tissue types fine-tune slo channel properties to the needs of a particular cell.
Similar articles
-
hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family.FEBS Lett. 2000 May 26;474(1):99-106. doi: 10.1016/s0014-5793(00)01584-2. FEBS Lett. 2000. PMID: 10828459
-
Cloning, expression, and distribution of a Ca(2+)-activated K+ channel beta-subunit from human brain.Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9200-5. doi: 10.1073/pnas.93.17.9200. Proc Natl Acad Sci U S A. 1996. PMID: 8799178 Free PMC article.
-
Properties of BK(Ca) channels formed by bicistronic expression of hSloalpha and beta1-4 subunits in HEK293 cells.J Membr Biol. 2003 Mar 15;192(2):141-8. doi: 10.1007/s00232-002-1070-0. J Membr Biol. 2003. PMID: 12682801
-
High-conductance calcium-activated potassium channels; structure, pharmacology, and function.J Bioenerg Biomembr. 1996 Jun;28(3):255-67. doi: 10.1007/BF02110699. J Bioenerg Biomembr. 1996. PMID: 8807400 Review.
-
International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels.Pharmacol Rev. 2017 Jan;69(1):1-11. doi: 10.1124/pr.116.012864. Epub 2016 Nov 15. Pharmacol Rev. 2017. PMID: 28267675 Free PMC article. Review.
Cited by
-
Large conductance, calcium- and voltage-gated potassium (BK) channels: regulation by cholesterol.Pharmacol Ther. 2012 Aug;135(2):133-50. doi: 10.1016/j.pharmthera.2012.05.002. Epub 2012 May 11. Pharmacol Ther. 2012. PMID: 22584144 Free PMC article. Review.
-
BK Channels in the Central Nervous System.Int Rev Neurobiol. 2016;128:281-342. doi: 10.1016/bs.irn.2016.04.001. Epub 2016 May 13. Int Rev Neurobiol. 2016. PMID: 27238267 Free PMC article. Review.
-
Single Channel Recordings Reveal Differential β2 Subunit Modulations Between Mammalian and Drosophila BKCa(β2) Channels.PLoS One. 2016 Oct 18;11(10):e0163308. doi: 10.1371/journal.pone.0163308. eCollection 2016. PLoS One. 2016. PMID: 27755549 Free PMC article.
-
Long-term hypoxia increases calcium affinity of BK channels in ovine fetal and adult cerebral artery smooth muscle.Am J Physiol Heart Circ Physiol. 2015 Apr 1;308(7):H707-22. doi: 10.1152/ajpheart.00564.2014. Epub 2015 Jan 16. Am J Physiol Heart Circ Physiol. 2015. PMID: 25599571 Free PMC article.
-
The brain-specific Beta4 subunit downregulates BK channel cell surface expression.PLoS One. 2012;7(3):e33429. doi: 10.1371/journal.pone.0033429. Epub 2012 Mar 16. PLoS One. 2012. PMID: 22438928 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
- Actions
- Actions
- Actions
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases