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Volume 272, Number 52, Issue of December 26, 1997
pp. 32723-32726
(Received for publication, October 3, 1997, and in revised form, October 23, 1997)
From the Target Discovery Department and the
We have isolated a novel gene, hKCa4,
encoding an intermediate conductance, calcium-activated potassium
channel from a human lymph node library. The translated protein
comprises 427 amino acids, has six transmembrane segments, S1-S6, and
a pore motif between S5 and S6. hKCa4 shares 41-42% similarity at the
amino acid level with three small conductance calcium-activated
potassium channels cloned from brain. Northern blot analysis of primary human T lymphocytes reveals a 2.2-kilobase transcript that is highly
up-regulated in activated compared with resting cells, concomitant with
an increase in KCa current. hKCa4 transcript is also
detected by Northern blots or by polymerase chain reaction in placenta,
prostate, thymus, spleen, colon, and many cell lines of hematopoietic
origin. Patch-clamp recordings of hKCa4-transfected HEK 293 cells reveal a large voltage-independent, inwardly rectifying potassium
current that is blocked by externally applied tetraethylammonium (Kd = 30 ± 7 mM), charybdotoxin
(Kd = 10 ± 1 nM), and
clotrimazole (Kd = 387 ± 34 nM),
but is resistant to apamin, iberiotoxin, kaliotoxin, scyllatoxin
(Kd > 1 µM), and margatoxin
(Kd > 100 nM). Single hKCa4 channels have a conductance of 33 ± 2 picosiemens in symmetrical potassium solutions. The channel is activated by intracellular calcium
(Kd = 270 ± 8 nM) with a highly
cooperative interaction of approximately three calcium ions per
channel. These properties of the cloned channel are very similar to
those reported for the native KCa channel in activated human T
lymphocytes, indicating that hKCa4 encodes this channel
type.
COMMUNICATION:
A Novel Gene, hKCa4, Encodes the Calcium-activated
Potassium Channel in Human T Lymphocytes
,
and
Respiratory, Inflammatory, and Neurological Diseases
Department, Zeneca Pharmaceuticals, Wilmington, Delaware 19850
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E. Cowley and P. Linsdell Characterization of basolateral K+ channels underlying anion secretion in the human airway cell line Calu-3 J. Physiol., December 19, 2001; (2001) 200101330. [Abstract] [PDF]
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R. Kohler, S. Brakemeier, M. Kuhn, C. Behrens, R. Real, C. Degenhardt, H.-D. Orzechowski, A. R. Pries, M. Paul, and J. Hoyer Impaired Hyperpolarization in Regenerated Endothelium After Balloon Catheter Injury Circ. Res., July 20, 2001; 89(2): 174 - 179. [Abstract] [Full Text] [PDF]
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