Abstract
The effect of the selective inhibitor of Na+/Ca2+ exchanger (NCX), KB-R7943, on large-conductance Ca2+-activated K+ (BKCa) channels was examined in cultured human umbilical vein endothelial cells (HUVECs) and freshly isolated mouse aortic smooth muscle cells (MASMCs). In voltage-clamped cells, KB-R7943 reversibly activated BKCa currents in HUVECs and MASMCs. The EC50 of KB-R7943 for BKCa current activation in HUVECs was determined to be 6.78 ± 0.7 μM. In inside-out and outside-out patches, KB-R7943 markedly increased BKCa channel activity and slightly decreased single channel current amplitudes. In inside-out patches, KB-R7943 shifted the relationship between [Ca2+]i and open probability (Po) to the left; the [Ca2+]i required to evoke half-maximal activation changed from 1220 ± 68 nM (in the absence of KB-R7943) to 620 ± 199 nM (in the presence of 10 μM KB-R7943). In addition, KB-R7943 shifted the relationship between membrane potential and Po to the left; the membrane potential to evoke half-maximal activation changed from 76.86 ± 1.09 mV (in the absence of KB-R7943) to 49.62 ± 2.55 mV (in the presence of 10 μM KB-R7943). In conclusion, KB-R7943 was found to act as a potent BKCa channel activator, which increases the sensitivity of BKCa channels to cytosolic free Ca2+ and membrane potential, and thereby BKCa channel activity. These results should be considered when KB-R7943 is used as NCX blocker.
| Original language | English |
|---|---|
| Pages (from-to) | 35-41 |
| Number of pages | 7 |
| Journal | European Journal of Pharmacology |
| Volume | 582 |
| Issue number | 1-3 |
| DOIs | |
| Publication status | Published - 2008 Mar 17 |
| Externally published | Yes |
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Keywords
- Endothelial cells
- KB-R7943
- Large-conductance Ca-activated K channels
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
The Na+/Ca2+ exchanger inhibitor KB-R7943 activates large-conductance Ca2+-activated K+ channels in endothelial and vascular smooth muscle cells. / Liang, Guo Hua; Kim, Ji Aee; Seol, Geun Hee; Choi, Shinkyu; Suh, Suk Hyo.
In: European Journal of Pharmacology, Vol. 582, No. 1-3, 17.03.2008, p. 35-41.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Na+/Ca2+ exchanger inhibitor KB-R7943 activates large-conductance Ca2+-activated K+ channels in endothelial and vascular smooth muscle cells
AU - Liang, Guo Hua
AU - Kim, Ji Aee
AU - Seol, Geun Hee
AU - Choi, Shinkyu
AU - Suh, Suk Hyo
PY - 2008/3/17
Y1 - 2008/3/17
N2 - The effect of the selective inhibitor of Na+/Ca2+ exchanger (NCX), KB-R7943, on large-conductance Ca2+-activated K+ (BKCa) channels was examined in cultured human umbilical vein endothelial cells (HUVECs) and freshly isolated mouse aortic smooth muscle cells (MASMCs). In voltage-clamped cells, KB-R7943 reversibly activated BKCa currents in HUVECs and MASMCs. The EC50 of KB-R7943 for BKCa current activation in HUVECs was determined to be 6.78 ± 0.7 μM. In inside-out and outside-out patches, KB-R7943 markedly increased BKCa channel activity and slightly decreased single channel current amplitudes. In inside-out patches, KB-R7943 shifted the relationship between [Ca2+]i and open probability (Po) to the left; the [Ca2+]i required to evoke half-maximal activation changed from 1220 ± 68 nM (in the absence of KB-R7943) to 620 ± 199 nM (in the presence of 10 μM KB-R7943). In addition, KB-R7943 shifted the relationship between membrane potential and Po to the left; the membrane potential to evoke half-maximal activation changed from 76.86 ± 1.09 mV (in the absence of KB-R7943) to 49.62 ± 2.55 mV (in the presence of 10 μM KB-R7943). In conclusion, KB-R7943 was found to act as a potent BKCa channel activator, which increases the sensitivity of BKCa channels to cytosolic free Ca2+ and membrane potential, and thereby BKCa channel activity. These results should be considered when KB-R7943 is used as NCX blocker.
AB - The effect of the selective inhibitor of Na+/Ca2+ exchanger (NCX), KB-R7943, on large-conductance Ca2+-activated K+ (BKCa) channels was examined in cultured human umbilical vein endothelial cells (HUVECs) and freshly isolated mouse aortic smooth muscle cells (MASMCs). In voltage-clamped cells, KB-R7943 reversibly activated BKCa currents in HUVECs and MASMCs. The EC50 of KB-R7943 for BKCa current activation in HUVECs was determined to be 6.78 ± 0.7 μM. In inside-out and outside-out patches, KB-R7943 markedly increased BKCa channel activity and slightly decreased single channel current amplitudes. In inside-out patches, KB-R7943 shifted the relationship between [Ca2+]i and open probability (Po) to the left; the [Ca2+]i required to evoke half-maximal activation changed from 1220 ± 68 nM (in the absence of KB-R7943) to 620 ± 199 nM (in the presence of 10 μM KB-R7943). In addition, KB-R7943 shifted the relationship between membrane potential and Po to the left; the membrane potential to evoke half-maximal activation changed from 76.86 ± 1.09 mV (in the absence of KB-R7943) to 49.62 ± 2.55 mV (in the presence of 10 μM KB-R7943). In conclusion, KB-R7943 was found to act as a potent BKCa channel activator, which increases the sensitivity of BKCa channels to cytosolic free Ca2+ and membrane potential, and thereby BKCa channel activity. These results should be considered when KB-R7943 is used as NCX blocker.
KW - Endothelial cells
KW - KB-R7943
KW - Large-conductance Ca-activated K channels
UR - http://www.scopus.com/inward/record.url?scp=39149125440&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39149125440&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2007.12.021
DO - 10.1016/j.ejphar.2007.12.021
M3 - Article
C2 - 18237728
AN - SCOPUS:39149125440
VL - 582
SP - 35
EP - 41
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -