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J Biol Chem, Vol. 275, Issue 9, 6453-6461, March 3, 2000
From the We present the cloning and characterization of
two novel calcium-activated potassium channel The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF209747 (for H
Cloning and Functional Characterization of Novel Large
Conductance Calcium-activated Potassium Channel
Subunits, hKCNMB3
and hKCNMB4*
,¶
Howard Hughes Medical Institute, Molecular
and Cellular Physiology, Stanford School of Medicine,
Stanford, California 94305 and § Icagen,
Durham, North Carolina 27703
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 subunits with the previously cloned mouse 1 (mKCNMB1) and the human 2 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 subunits on some Hslo1 channel
properties are calcium-dependent. mKCNMB1 and hKCNMB2 slow
activation at 1 µM but not at 10 µM free
calcium concentrations. hKCNMB4 decreases Hslo1 channel
openings at low calcium concentrations but increases channel openings
at high calcium concentrations. These results suggest that subunits
in diverse tissue types fine-tune slo channel properties to
the needs of a particular cell.
*
This work was supported by Grant NS23294 from the National
Institutes of Health and by Grant MH48108 from the National Institute of Mental Health Silvio Conte Center for Neuroscience Research.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
2), AF214561 (for H3), and AF207992 for
(H4).
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