Functional evidence of a role for two‐pore domain potassium channels in rat mesenteric and pulmonary arteries

British Journal of Pharmacology - Tập 142 Số 1 - Trang 192-202 - 2004
M J Gardener1,2, Ian T. Johnson1,2, Matthew Burnham2, G. Edwards2, Anthony M. Heagerty3, A.H. Weston2
1Both authors contributed equally to this study.
2School of Biological Sciences, Stopford Building, University of Manchester, Manchester M13 9PT
3Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL

Tóm tắt

Experiments were performed to elucidate the mechanism by which alterations of extracellular pH (pHo) change membrane potential (EM) in rat mesenteric and pulmonary arteries. Changing pHo from 7.4 to 6.4 or 8.4 produced a depolarisation or hyperpolarisation, respectively, in mesenteric and pulmonary arteries. Anandamide (10 μM) or bupivacaine (100 μM) reversed the hyperpolarisation associated with alkaline pHo, shifting the EM of both vessels to levels comparable to that at pH 6.4. In pulmonary arteries, clofilium (100 μM) caused a significant reversal of hyperpolarisation seen at pH 8.4 but was without effect at pH 7.4. K+ channel blockade by 4‐aminopyridine (4‐AP) (5 mM), tetraethylammonium (TEA) (10 mM), Ba2+ (30 μM) and glibenclamide (10 μM) depolarised the pulmonary artery. However, shifts in EM with changes in pHo remained and were sensitive to anandamide (10 μM), bupivacaine (100 μM) or Zn2+ (200 μM). Anandamide (0.3–60 μM) or bupivacaine (0.3–300 μM) caused a concentration‐dependent increase in basal tone in pulmonary arteries. RT–PCR demonstrated the expression of TASK‐1, TASK‐2, THIK‐1, TRAAK, TREK‐1, TWIK‐1 and TWIK‐2 in mesenteric arteries and TASK‐1, TASK‐2, THIK‐1, TREK‐2 and TWIK‐2 in pulmonary arteries. TASK‐1, TASK‐2, TREK‐1 and TWIK‐2 protein was demonstrated in both arteries by immunostaining. These experiments provide evidence for the presence of two‐pore domain K+ channels in rat mesenteric and pulmonary arteries. Collectively, they strongly suggest that modulation of TASK‐1 channels is most likely to have mediated the pH‐induced changes in membrane potential observed in these vessels, and that blockade of these channels by anandamide or bupivacaine generates a small increase in pulmonary artery tone. British Journal of Pharmacology (2004) 142, 192–202. doi:10.1038/sj.bjp.0705691

Từ khóa


Tài liệu tham khảo

10.1016/S0014-5793(98)00260-9

10.1016/0003-2697(76)90527-3

10.1111/j.1476-5381.1988.tb11752.x

10.1007/BF00497774

10.1016/S0014-5793(01)02222-0

10.1152/ajpheart.1998.275.3.H887

10.1016/S0169-328X(01)00330-8

GARDENER M.J., 2003, Functional evidence for the presence of TASK‐1 in the rat mesenteric artery, Br. J. Pharmacol. Proc. Supp.

10.1046/j.1440-1681.2002.03653.x

10.1161/01.RES.0000099883.68414.61

JOHNSON I.T., 2003, Evidence for the involvement of TASK‐1 in setting resting membrane potential and resting tension in the rat small pulmonary artery, Br. J. Pharmacol. Proc. Supp.

10.1152/ajpheart.00963.2001

10.1038/376690a0

10.1006/bbrc.2001.5064

10.1016/S0169-328X(00)00136-4

10.1097/00000542-199904000-00024

10.1111/j.1462-5822.2007.00901.x

10.1523/JNEUROSCI.18-03-00868.1998

10.1002/j.1460-2075.1996.tb00437.x

10.1152/ajprenal.2000.279.5.F793

10.1074/jbc.C100184200

10.1093/emboj/20.1.47

10.1177/22.12.1077

10.1074/jbc.M107192200

10.1016/S0005-2736(02)00597-7

10.1038/sj.bjp.0702006

10.1152/ajplung.1998.275.6.L1069

10.1016/S0166-2236(00)01810-5

10.1152/ajpheart.1998.274.2.H655

10.1074/jbc.273.47.30863

10.1111/j.1469-445X.1999.01864.x

10.1073/pnas.76.9.4350

Thông tin
Thông tin xuất bản

British Journal of Pharmacology

Tập 142 Số 1

192-202

Thông tin tác giả