Selective activation of heterologously expressed G protein-gated K+ channels by M2 muscarinic receptors in rat sympathetic neurones

被引:41
作者
Fernandez-Fernandez, JM
Wanaverbecq, N
Halley, P
Caulfield, MP
Brown, DA
机构
[1] UCL, Dept Pharmacol, London WC1E 6BT, England
[2] Univ Dundee, Ninewells Hosp & Med Sch, Dept Pharmacol & Neurosci, Dundee DD1 9SY, Scotland
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1999年 / 515卷 / 03期
基金
英国惠康基金;
关键词
D O I
10.1111/j.1469-7793.1999.631ab.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1 protein-regulated inward rectifier Kf (GIRK) channels were over-expressed in dissociated rat superior cervical sympathetic (SCG) neurones by co-transfecting green fluorescent protein (GFP)-, GIRK1- and GIRK2-expressing plasmids using the biolistic technique. Membrane currents were subsequently recorded with whole-cell patch electrodes. 2. Co-transfected cells had larger Ba2+-sensitive inwardly rectifying currents and 13 mV more negative resting potentials (in 3 mM [K+](0)) than non-transfected cells, or cells transfected with GIRK 1 or GIRK2 alone. 3. Carbachol (CCh, 1-30 mu m) increased the inwardly rectifying current in 70% of GIRK1+ GIRK2-transfected cells by 261 +/- 53% (n = 6, CCh 30 mu m) at -120 mV, but had no effect in non-transfected cells or in cells transfected with GIRK1 or GIRK2 alone. Pertussis toxin prevented the effect of carbachol but had no effect on basal currents. 4. The effect of CCh was antagonized by 6 nM tripitramine but not by 100 nM pirenzepine, consistent with activation of endogenous M-2, muscarinic acetylcholine receptors. 5. In contrast, inhibition of the voltage-activated Ca2+ current by CCh was antagonized by: 100 nM pirenzepine but not by 6 nM tripitramine, indicating that it was mediated by M-4 muscarinic acetylcholine receptors. 6. We conclude that endogenous M-2 and M-4 muscarinic receptors selectively couple to GIRK currents and Ca2+ currents respectively; with negligible cross-talk.
引用
收藏
页码:631 / 637
页数:7
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