Activation of muscarinic m5 receptors inhibits recombinant KCNQ2/KCNQ3 K+ channels expressed in HEK293T cells

被引:11
作者
Guo, J [1 ]
Schofield, GG [1 ]
机构
[1] Tulane Univ, Ctr Hlth Sci, Dept Physiol SL39, New Orleans, LA 70112 USA
关键词
K+ current; M-current; oxo-tremorine M; muscarinic receptor; channel expression;
D O I
10.1016/S0014-2999(03)01323-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A variety of G-protein-coupled receptors regulate membrane excitability via M-type K+ current (M-current) modulation. Muscarinic m1 and m3 acetylcholine receptors have both been implicated in the modulation of M-current. The muscarinic m5 receptor, like muscarinic m1 and m3 receptors, couples to phospholipase C via a pertussis toxin-insensitive G protein. Since a number of other receptors which activate phospholipase C also modulate M-current, we investigated if muscarinic m5 receptors could modulate recombinant M-type (KCNQ2/KCNQ3) K+ channels after heterologous expression in human embryonic kidney (HEK) 293T cells. Application of Oxo-tremorine M to HEK293T cells expressing muscarinic m1, m3, or m5 receptors produced a similar robust inhibition of M-current, whereas muscarinic m2 and m4 receptor stimulation was without effect. Muscarinic m1, m3, or m5 receptor stimulation decreased the deactivation time constants of M-current at - 50 mV. The inhibition of M-current by stimulation of muscarinic m1, m3, or m5 receptors was insensitive to overnight treatment with pertussis toxin or cholera toxin, which interfere with G(j/o). and G(s) G-protein signaling. These data suggest that muscarinic m1, m3, and m5 receptors inhibit M-channels via the activation of a common G protein. (C) 2003 Elsevier Science B.V All rights reserved.
引用
收藏
页码:25 / 32
页数:8
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